Meningococcus

Acta Pathol Microbiol Immunol Scand {C}, 1985 Jun, 93(3), 143 - 4
Purification of anti-lactose antibodies from antisera to Neisseria gonorrhoeae and Neisseria meningitidis; Brakstad OG et al.; Lactosyl-sepharose 4B columns were used for purification by affinity chromatography of anti-lactose antibodies from rabbit antisera to the gonococcal strains 8551 and VII, and the serogroup B meningococcal strain M982 . Anti-lactose antibodies were obtained from all three antisera . SDS-PAGE of lipopolysaccharide and of bacterial cells and immunoblotting with the anti-lactose antibodies showed that the lipopolysaccharide was the only bacterial component with binding sites for the antibodies.

J Hyg (Lond), 1985 Jun, 94(3), 279 - 88
Carriage of Neisseria meningitidis and Neisseria lactamica in a school population during an epidemic period in Spain; Saez-Nieto JA et al.; A study was made of the incidence of Neisseria meningitidis and N . lactamica in a school population; 2470 children aged between 5 and 7 years were studied from four schools in Alcala de Henares (Madrid) . Nasopharyngeal swabs were taken in June, November and March, between 1979 and 1983 . In all the surveys except one, the proportion of carriers of N . lactamica was higher than that of N . meningitidis, reaching a ratio of about 2:1 in the complete study . The predominant serogroup of meningococcus found was B (41%), with nongroupable strains reaching 43% . A study of serotypes within group B showed a predominance of nontypable strains (48.5%), while those strains considered to be most virulent (types 2 and 1, 8, 15) reached 40% . Eighteen per cent of N . lactamica strains were observed to agglutinate with antimeningococcal sera whilst the remainder of the strains were rough . When these strains were studied with the antiserum-agar technique, using antimeningococcal sera, a high percentage of strains cross-reacted with the meningococci . The susceptibility of strains to sulphadiazine, penicillin, ampicillin, chloramphenicol, rifampicin and spiramycin was determined . Finally an analysis was made of the effect that an elevated colonization rate of N . lactamica might have on colonization by meningococci . The necessity of using fine epidemiological markers in tracing virulent strains in a population at risk is stressed . Selective prophylactic measures are also necessary.

J Exp Med, 1985 Jun 1, 161(6), 1539 - 53
Pili of Neisseria meningitidis . Analysis of structure and investigation of structural and antigenic relationships to gonococcal pili; Stephens DS et al.; To provide information useful for the design of a pilus vaccine effective for the prevention of both meningococcal and gonococcal disease, the electron microscopic morphology of meningococcal pili and the structural and antigenic relationships of meningococcal pili to gonococcal pili were investigated . Meningococcal pili were 4-6 nm in width, extended 500-6,000 nm from the organism surface, and occurred singly or in bundles composed of 8-10 pili per bundle . Meningococcal pilin varied between 17,250 and 20,600 daltons . Pilin was present in outer membrane preparations of some meningococcal isolates that were nonpiliated by electron microscopic examination . Antibodies to gonococcal pili, cyanogen bromide cleavage fragments of gonococcal pilin, or synthetic peptide analogues corresponding to regions of the gonococcal pilin sequence, were used to detect common meningococcal and gonococcal antigenic determinants that might indicate the existence of a conserved sequence beyond residue 29 . Antibody to intact gonococcal pili or to the variable CNBR-3 region of gonococcal pilin detected little shared antigenicity with meningococcal pilin . However, pilin from all tested meningococcal isolates reacted with antibody to the CNBR-2 fragment of gonococcal pilin, a region highly conserved among gonococcal strains . Meningococcal pilins were also broadly crossreactive with antibody to a synthetic peptide corresponding to residues 69-84 of the gonococcal sequence, a part of the CNBR-2 region that appears to be critical for gonococcal receptor-binding function . If a sequence similar to 69-84 is also important for receptor-binding function in meningococcal pili, a peptide corresponding to this region may elicit antibodies that block the adherence function of pili elaborated by both Neisseria gonorrhoeae and N . meningitidis.

Med Clin North Am, 1985 May, 69(3), 487 - 504
The hereditary and acquired deficiencies of complement; Nusinow SR et al.; The identification of hereditary and acquired complement deficiencies in humans has led to a better understanding of the biologic importance of the complement system in immunity and autoimmune disease . Although the understanding of the relevance of complement in the pathogenesis of disease is incomplete, several characteristic clinical syndromes associated with complement deficiencies have been recognized and should be known to the practicing clinician . In allergic diseases, one need recognize the C1 inhibitor deficiency syndromes which can present as severe, recurrent angioedema in childhood or in the adult as recurrent angioedema in association with a lymphoid malignancy or autoimmune disease . Complement analyses allow one to readily diagnose C1 inhibitor deficiency in angioedema . Correct diagnosis is critical because safe effective therapy is available . Chronic urticaria is also uncommonly associated with complement deficiencies, particularly acquired C1q deficiency . Again, effective therapy for hypocomplementemic urticarial vasculitis and C1q deficiency is available and differs significantly from the usual management of chronic urticaria . Homozygous and acquired deficiencies of C3 are associated with severe immune deficiency and recurrent infections with gram-positive and gram-negative bacteria . Recurrent meningococcemia and gonococcemia are being identified frequently in patients with a deficient membrane attack mechanism relating to deficiency of C5, C6, C7, or C8 . Nearly one third of the patients developing meningococcemia may have an associated complement deficiency indicating the importance of complement determinations in understanding the treatment and prognosis for these patients . Deficiency of almost every complement component has been reported in association with one or more rheumatic diseases, particularly systemic lupus erythematosus . Extensive studies of C2 deficiency and limited studies of C4 deficiency indicate that these components of the classical pathway of complement are important in preventing the development of SLE or are linked to other genes predisposing to SLE . The clinical presentations of SLE in association with C2 or C4 deficiency are relatively uniform . The patients exhibit typical skin manifestations suggestive of SLE and DLE and often exhibit antibodies to SSA (Ro) . The association of complement deficiencies with clinical syndromes is important for today's physician . The syndromes and deficiencies described here are the beginning of an expanding knowledge relating to the pathobiology of complement in human disorders.

J Clin Microbiol, 1985 May, 21(5), 734 - 7
Evaluation of the RIM-N, Gonochek II, and Phadebact systems for the identification of pathogenic Neisseria spp . and Branhamella catarrhalis; Janda WM et al.; Methods for identifying Neisseria spp . include conventional and modified carbohydrate degradation procedures, chromogenic enzyme substrate tests, and immunologic coagglutination tests for Neisseria gonorrhoeae . In this study, we evaluated the abilities of the RIM-N carbohydrate degradation system (American MicroScan, Campbell, Calif.), the Gonochek II enzymatic identification system (Du Pont Co., Wilmington, Del.), and the Phadebact Gonococcus coagglutination test (Pharmacia Diagnostics, Piscataway, N.J.) to identify pathogenic Neisseria spp . and Branhamella catarrhalis . Both stock strains and clinical isolates, including 176 N . gonorrhoeae, 173 Neisseria meningitidis, 48 Neisseria lactamica, and 12 B . catarrhalis strains, were tested . The RIM-N identified 98% of the gonococci, 99% of the meningococci, 94% of the N . lactamica strains, and 100% of the B . catarrhalis strains within 1 h . The Gonochek II system identified 99% of the gonococci, 97% of the meningococci, 100% of the N . lactamica strains, and 100% of the B . catarrhalis strains within 30 min . Phadebact coagglutination provided clearly positive results for only 77% of the N . gonorrhoeae strains, producing negative or equivocal results with 23% of the strains . The RIM-N and Gonocheck II tests generally produced clear-cut reactions . An additional advantage of the Gonocheck II system was the small inoculum required for the performance of the test compared with the other systems, thus allowing the identification of N . gonorrhoeae directly from the primary isolation medium.

Infect Immun, 1985 May, 48(2), 428 - 32
Immunoresponses to Neisseria meningitidis epitopes: primary versus secondary antiphosphorylcholine responses; Faro J et al.; Specific antiphosphorylcholine immune responses were found to be elicited by different Neisseria meningitidis group B M986 preparations . Our results suggest the functional presence of phosphorylcholine in the bacteria . The immune responses, mostly immunoglobulin M, were measured with a plaque-forming cell assay . The secondary phosphorylcholine-specific immune response induced by intact meningococci was significantly lower than the primary phosphorylcholine-specific immune response induced by the same antigens . This suppression is priming time dependent and does not represent an early switching to the expression of other classes of immunoglobulins.

Infect Immun, 1985 May, 48(2), 336 - 42
Structural and antigenic analysis of meningococcal piliation; Olafson RW et al.; Pilin with an Mr of 16,500 was purified to homogeneity from Neisseria meningitidis SP3428 . Procedures which provided useful separation during purification included high-pressure liquid chromatography with a TSK size exclusion column, Sephacryl S-200 column chromatography, ion-exchange chromatography with SP-Sephadex, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis . The amino acid composition of this pilin was similar to that previously reported for this species . The sequence of N-terminal 51 amino acids was also determined . The protein lacked a modified phenylalanine at the amino terminus and displayed six residues which were different from Neisseria gonorrhoeae in that region of the molecule determined to be the lectin-binding domain . Monoclonal antibody raised to this pilin was employed, along with a monoclonal antibody to an epitope common to all gonococcal pilins, to analyze the intra- and interstrain heterogeneity of meningococcal piliation . The results indicate that N . meningitidis displays considerable intra- and interstrain heterogeneity with respect to both pilus subunit size and antigenicity . The Mr of subunits ranged from 13,000 to 20,000.

Zh Mikrobiol Epidemiol Immunobiol, 1985 Apr, (4), 66 - 9
{Modification of an immunoradiometric analysis method and the coagglutination reaction in the diagnosis of meningitis}; Alekseeva NV et al.; The coagglutination test and the radio-immunoassay (RIA) in the authors' modification have been used for the rapid diagnosis of meningococcal meningitis . This modification of RIA has been found to be highly sensitive with respect to soluble microbial antigens . In the study of liquors from patients with acute meningitides of different etiology RIA has been shown to have a higher efficiency in comparison with the coagglutination test . The data thus obtained indicate good prospects for the use of RIA in experimental and diagnostic investigations.

Clin Exp Immunol, 1985 Apr, 60(1), 183 - 90
Inherited C8 beta subunit deficiency in a patient with recurrent meningococcal infections: in vivo functional kinetic analysis of C8; Rao CP et al.; A 16 year old with recurrent meningococcal infections is reported . Absence of haemolytic activity in both the classical and alternative pathways resulted from an absence of functional C8 . Addition of functional C8 restored hemolytic activity . Antigenically deficient C8 was present in the serum and isoelectric focusing of serum confirmed the absence of the C8 beta chain . Following the infusion of fresh frozen plasma, we followed the decay in C8 functional activity as well as total haemolytic activity . C8 activity peaked at about 3 h with a half-life survival estimated to be 28 h . The kinetics of total haemolytic activity showed a slower decay with an exponential decline over 72 h and a half-life of 55 h . Fresh frozen plasma may be of value in the treatment of patients with C8 deficiency and acute Neisserial infections.

J Med Microbiol, 1985 Apr, 19(2), 203 - 9
Colony variants of Neisseria meningitidis strain 2996 (B:2b:P1.2): influence of class-5 outer membrane proteins and lipopolysaccharides; Poolman JT et al.; Different colonial morphologies were found among colonies of Neisseria meningitidis strain 2996 (B:2b:P1.2) . Examination of cultures, selected on the basis of colony transparency or opacity, revealed that both lipopolysaccharides (LPS) and class-5 outer membrane proteins (OMP) are associated with differences in colonial morphology . Among 13 variants, four LPS variants and two class-5 OMP variants were recognised . All variants were non-fimbriate . The LPS variations were confirmed by immunoprecipitation . In addition to these qualitative variations of LPS, meningococci synthesise LPS of different molecular size depending upon growth phase; larger LPS molecules were found after analysis of stationary-phase cultures than with exponential-phase cultures . These changes did not cause a change in serotyping characteristics . The recognition in this study of intra-strain heterogeneity of meningococcal LPS and class-5 OMPs is important for the understanding of meningococcal pathogenicity . This heterogeneity was also detected in simultaneous isolates from different sites of a patient.

Infect Immun, 1985 Apr, 48(1), 23 - 8
Recognition of serogroup A Neisseria meningitidis serotype antigens by human antisera; Sugasawara RJ; The antigens of Neisseria meningitidis serogroup A which were recognized by human antisera were identified by Western blot and enzyme-linked immunosorbent assay techniques . The components of six prototype strains used for serotyping serogroup A meningococci were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then transferred to nitrocellulose for immunoperoxidase staining with sera collected from 10 acute-phase and 14 convalescent-phase patients . Six acute-phase sera detected six major antigens having apparent molecular weights between 14,000 and 82,000 . In addition to recognizing these antigens, the convalescent-phase sera detected a protease-sensitive antigen with an apparent molecular weight of 20,000 for one strain and 27,000 for five strains, lipopolysaccharide, and the heat-modifiable proteins . The sera recognized lipopolysaccharide in a serotype-specific manner, whereas their reactions with the heat-modifiable protein were not serotype specific . Convalescent-phase sera recognized components from eight meningococcal serogroups . The concentrations of immunoglobulin G directed to capsular polysaccharide were determined by the enzyme-linked immunosorbent assay; seven acute-phase sera had less than 0.39 micrograms of antibody per ml, whereas the average concentration in convalescent-phase sera was 3.22 micrograms/ml and the range was 0.40 to 7.50 micrograms/ml.

J Infect Dis, 1985 Apr, 151(4), 650 - 7
Neisserial antigen H.8 is immunogenic in patients with disseminated gonococcal and meningococcal infections; Black JR et al.; Antigenic diversity among and within strains of Neisseria gonorrhoeae and Neisseria meningitidis has complicated studies of the pathogenesis of these strains and obstructed vaccine development . We previously described a distinct surface antigen (H.8) common to pathogenic Neisseria . We have now demonstrated in vivo expression of the H.8 antigen by detecting antibody responses to the antigen in 13 patients with disseminated neisserial infections . Each serum sample from a convalescent patient blocked the binding between the infecting meningococcal or gonococcal strain and a monoclonal antibody directed to the H.8 antigen, as demonstrated by binding-inhibition studies in enzyme-linked immunosorbent assays (P less than .005) . Testing by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting demonstrated an IgG response in each convalescent serum to an antigen co-migrating with the H.8 antigen . Specificity of this antibody response was confirmed by probing recombinant bacteriophage that expressed the H.8 antigen . The commonality and the immunogenicity of the H.8 antigen indicate its possible role in the pathogenesis of, and its potential as a vaccine component for, gonococcal and meningococcal diseases.

Helv Paediatr Acta, 1985 Apr, 40(1), 9 - 16
{Current therapy of meningococcal infection in childhood}; Sutter MU; The article discusses the present therapy of acute meningococcal septicemia . Besides adequate antibiotic treatment, the importance of early and aggressive shock and respiratory therapy, i.e . endotracheal intubation and mechanical ventilation, is stressed . The role of corticosteroids is discussed . The use of anticoagulants, fibrinolytic agents and inhibitors of fibrinolysis is discouraged.

Sex Transm Dis, 1985 Apr-Jun, 12(2), 88 - 9
Postmeningococcal urethritis caused by Chlamydia trachomatis: a case report; Lefevre JC et al.; The authors describe a case of meningococcal urethritis that was followed, after treatment with spectinomycin, by development of urethritis due to Chlamydia trachomatis . This case report emphasizes the need for thorough differentiation of species of Neisseria and of direct microbiologic diagnosis of chlamydial infection in laboratories.

J Immunol, 1985 Apr, 134(4), 2651 - 7
Determinant specificities of the groups B and C polysaccharides of Neisseria meningitidis; Jennings HJ et al.; A meningococcal group B-specific horse antiserum contains at least two distinct populations of antibodies with specificities for determinants on the group B capsular polysaccharide antigen . These two populations were differentiated on the basis of the ability of only one of them to be absorbed from the antiserum by the structurally related colominic acid . The nature of the colominic acid-specific determinant was elucidated by a radioimmunoassay inhibition technique with the use of a series of linear alpha-(2----8)-linked oligomers of sialic acid as inhibitors . Colominic acid was labeled by prior removal of its N-acetyl groups, followed by their replacement with the use of {3H}acetic anhydride . The conformational nature of the determinant was proposed because of the unusually large size (10 sialic acid residues) of the oligomer required to function as an efficient inhibitor . The structure of the determinant responsible for the second population of group B-specific antibodies has not been determined, but it is obviously based on an as yet undefined conformational or structural feature peculiar to the group B meningococcal polysaccharide . In contrast to the colominic acid-specific group B determinant, the determinant responsible for the group C polysaccharide-specific rabbit antibodies proved to be more conventional . Inhibitory properties of the alpha-(2----9)-linked oligomers maximized with those containing four or five sialic acid residues, which is consistent with the approximate estimated maximal size of an antibody site.

Zh Mikrobiol Epidemiol Immunobiol, 1985 Apr, (4), 63 - 6
{Increased specificity of immunoenzyme analysis for diagnosing meningococcal infection}; Zhuravleva GV et al.; The ELISA test system for the detection of polysaccharide antigens of meningococci, groups A and C, on the basis of the neutralization of specific antibodies has been developed . The specificity of this reaction is determined by the chemically pure preparations of group A and C meningococcal polysaccharides . The sensitivity of this test system based on the neutralization of antibodies is not inferior to that of ELISA with the use of double antiserum.

MMWR Morb Mortal Wkly Rep, 1985 Mar 8, 34(9), 119 - 20, 125
Epidemic meningococcal disease: recommendations for travelers to Nepal; Immune complexes and the pathogenesis of meningococcal arthritis; Immune complex levels were measured in serum and synovial fluid obtained from 10 patients who developed arthritis 3-8 days after the onset of meningococcal meningitis . Mean serum immune complex levels were lower in these patients than in eight age matched control patients with meningococcal disease who did not develop late complications . This observation suggests that meningococcal arthritis follows local formation of immune complexes in the synovium rather than deposition of circulating immune complexes . Purified meningococcal polysaccharide antigen-induced synovitis when injected into the knee of rabbits previously sensitized by i.v . injection with heat killed meningococci.

J Clin Microbiol, 1985 Mar, 21(3), 464 - 6
Neisseria meningitidis serogroup 29E (Z') septicemia in a patient with far advanced multiple myeloma (plasma cell leukemia); Wachter E et al.; A case of septicemia caused by Neisseria meningitidis serogroup 29E (Z') in a patient with plasma cell leukemia is described . The patient developed disseminated intravascular coagulation, had a cardiopulmonary arrest, and died . The effects of altered immune function leading to a predisposition to meningococcal infections are discussed.

Schweiz Med Wochenschr, 1985 Feb 23, 115(8), 281 - 4
{Acute myocardial dysfunction in meningococcal septicemia}; Horisberger JD et al.; A progressive myocardial dysfunction is known to occur in prolonged septic shock . The cases of two patients with acute meningococcal infection and Waterhouse-Friderichsen syndrome are reported . Hemodynamic measurements showed, in the early stage, the classical picture of hyperdynamic septic shock, with increased cardiac output and low systemic vascular resistances . However, rapidly progressive cardiac failure then occurred, with high filling pressures and low cardiac output . One patient went into irreversible shock . In the other the administration of inotropic agents was beneficial, with a slow but progressive improvement in left ventricular function over several weeks . Acute myocarditis has been frequently observed in patients with meningococcal infections . It is suggested that the acute myocardial failure observed in those circumstances is caused by the myocarditis.

Proc Natl Acad Sci U S A, 1985 Feb, 82(4), 1194 - 8
NZB mouse system for production of monoclonal antibodies to weak bacterial antigens: isolation of an IgG antibody to the polysaccharide capsules of Escherichia coli K1 and group B meningococci; Frosch M et al.; A system for the production of monoclonal antibodies, particularly of the IgG type, against weakly immunogenic bacterial polysaccharide antigens is described . This system, which is based on the autoimmune NZB mouse strain, has been used to produce a monoclonal IgG2a antibody against the meningococcus group B and Escherichia coli K1 polysaccharides, identical homopolymers of alpha (2----8)-linked units of N-acetylneuraminic acid that are extremely poor immunogens . Comparison of the humoral immune responses of normal BALB/c mice and autoimmune NZB mice to hyperimmunization with group A, B, and C meningococci showed that, although both strains mounted a weak meningococcal B polysaccharide-specific IgM response, only the NZB strain mounted an IgG response . Similarly, NZB mice mounted a stronger IgG response to the more immunogenic group C meningococcal polysaccharide than did BALB/c mice, although this difference was less pronounced than that observed with meningococcal B polysaccharide . No difference between the two strains of mice was demonstrable with the strongly antigenic group A meningococcal polysaccharide . These results indicate that the NZB system may be generally useful for the production of monoclonal antibodies against weakly antigenic bacterial determinants.

Infect Immun, 1985 Feb, 47(2), 465 - 71
Influence of nutrient limitation and low pH on serogroup B Neisseria meningitidis capsular polysaccharide levels: correlation with virulence for mice; Masson L et al.; Neisseria meningitidis strain M986, which possesses a polyanionic sialic acid capsular polysaccharide, was resistant to the bactericidal effects of normal rabbit serum, but sensitive when immune serum and complement were present . An isogenic strain PRM102, deficient in the ability to produce capsular polysaccharide, was sensitive to normal serum . Strain M986, when grown under conditions of low pH or nutrient limitation, synthesized increased levels of capsular polysaccharide . This was accompanied by an increase in cell surface hydrophilicity and virulence for mice . Cells grown in low-pH, iron-limited medium synthesized the highest concentration of polysaccharide and exhibited the highest cell surface hydrophilicity and virulence among the cases examined . The increase in capsular polysaccharide was partly explained by a decrease in the specific activity of a membrane-bound cytidine monophosphate-N acetylneuraminic acid hydrolase . The results suggest that conditions of nutrient limitation and low pH exert profound effects on the physicochemical nature of the meningococcal cell surface which, in turn, cumulate in enhanced virulence of this organism for mice.

J Biol Chem, 1985 Jan 25, 260(2), 1265 - 70
Cleavage of the polysialosyl units of brain glycoproteins by a bacteriophage endosialidase . Involvement of a long oligosaccharide segment in molecular interactions of polysialic acid; Finne J et al.; Polysialosyl chains containing alpha 2-8-linked N-acetylneuraminic acid have been suggested to modulate the biological activity of a neural cell adhesion molecule . Polysialosyl glycopeptides isolated from developing brain were incubated with a bacteriophage containing endosialidase . Sialic acid oligomers up to 7 residues long were liberated both from the glycopeptides and colominic acid . The substrate specificity of the endosialidase was studied with sialic acid oligomers of different sizes prepared from colominic acid . It was found that the endosialidase required the simultaneous presence adjacent to the site of cleavage a minimum of 3 sialic acid residues on the distal side and a minimum of 5 sialic acid residues on the proximal (reducing end) side . From the fragments liberated by the enzyme the existence of polysialic acid chains up to at least 12 residues long in the glycopeptides were concluded . This was also supported by the interaction of the glycopeptides with a meningococcal group B polysaccharide antiserum, which was found to require 10 residues or more for binding . The results indicate that the brain polysialosyl glycopeptides contain a long polysialic acid segment, which is also specifically needed for certain molecular interactions . The implications of the findings for the biological properties of the neural cell adhesion molecule are discussed.

S Afr Med J, 1985 Jan 5, 67(1), 7 - 9
Meningococcal arthritis; Bhettay E et al.; Meningococcal infection (MI) remains endemic in the Western Cape . A review of 2216 cases in which the condition was diagnosed and notified to the relevant authorities between January 1977 and March 1982 is presented . In 121 patients the disease was complicated by meningococcal arthritis (MA) . MI and MA occurred most commonly in the Coloured population; over 50% of patients with MI were less than 2 years of age; and patients with MA were slightly older than the sample mean . The onset of arthritis showed a biphasic pattern with an early peak at 1-2 days and a later peak, heralded by typical recrudescence of fever, at 5-10 days which usually lasted 5-7 days . It was most often monarticular, the knee being the joint most frequently affected . Four cases of isolated MA were also encountered.

Arkh Patol, 1985, 47(10), 7 - 16
{Current problems in the pathological anatomy of acute neuroinfections in children}; Tsinzerling VA; The analysis of the autopsy material of children dying from acute neuroinfections in a specialized department of the Research Institute of Children's Infections from 1954 to 1984 is presented . The increase of the importance of hypertoxic forms of meningococcal infection, purulent meningoencephalitis (particularly those of pneumococcal etiology) as well as acute viral encephalitis (particularly herpetic ones) is noted at present . The results of the materials studied by the author from 182 children dying of those infections at the period from 1971 to 1984, the problems of their patho- and tanatogenesis are discussed . Special attention is drawn to the necessity of considering the type of an etiological agent, its properties, the features of tissue response and those of the immunological resistance in the brain for the diagnosis and epicritic assessment of acute neuroinfections.

J Infect, 1985 Jan, 10(1), 51 - 6
Meningococcal endocarditis with profound acquired hypocomplementaemia; Weetman AP et al.; A patient is described who presented with chronic endocarditis, due to Neisseria meningitidis, affecting a previously normal mitral valve . The illness was associated with glomerulonephritis that caused renal impairment and the nephrotic syndrome . Despite antibiotic treatment and replacement of the mitral valve, serum complement values remained very low, only returning to normal when immune complexes and a type III cryoglobulin disappeared from the circulation three months after resection of the valve vegetation . Such acquired hypocomplementaemia may have contributed to the chronicity of the disease process in this patient.

Biomed Pharmacother, 1985, 39(4), 167 - 70
Factors influencing host susceptibility to meningococcal disease; Winstanley FP et al.; Host-parasite interactions influencing the development of the protective humoral immune response to Neisseria meningitidis are briefly reviewed . Possible consequences of the observed decreased titres of bactericidal activity specific for meningococcal serogroups A, B and C among patients with gonorrhoea are discussed with reference to: the epidemiology of the two diseases, the protective role of "natural" antibodies to the Neisseria species and the carriage rate of serogroupable strains of N . meningitidis among patients with gonorrhoea and a control population.

Infect Control, 1985 Jan, 6(1), 37 - 40
Neisseria meningitidis; Stephens DS; N . meningitidis continues to be a worldwide cause of human disease, usually in otherwise healthy individuals . The natural habitat and reservoir for meningococci are the mucosal surfaces of the human nasopharynx and to a lesser extent, the urogenital tract and anal canal . In most instances meningococcal colonization of mucosal surfaces is asymptomatic but may produce local infection . In those individuals who lack serum bactericidal activity against the meningococcus, colonization of mucosal surfaces and bloodstream invasion by N . meningitidis can lead to devastating meningitis and septicemia . Recent studies on the ultrastructure of the meningococcus and on the mechanisms of pathogenesis have given us new insight into meningococcal infections and suggest ways for improved immunoprophylaxis . Currently, penicillin is the drug of choice for the treatment of meningococcal meningitis and septicemia . However, the report of meningococci with antibiotic resistant plasmids is alarming and in the future may alter traditional treatment regimens.

Scand J Clin Lab Invest Suppl, 1985, 178, 53 - 5
Plasmapheresis in the treatment of severe meningococcal or pneumococcal septicaemia with DIC and fibrinolysis . Preliminary data on eight patients; Brandtzaeg P et al.; Plasmapheresis (50 ml fresh frozen plasma/kg body weight per session--total 9-11 liters) was performed within 36 hours of the onset of septicaemia in 7 patients (1 woman and 6 men, age 14-48 years) . One 8 year old girl was treated with exchange blood transfusion (2 liters) . All had symptoms of severe septic shock caused by Neisseria meningitidis (6) or by Streptococcus pneumoniae (2) . All patients demonstrated signs of DIC and concomitant fibrinolysis with low platelet values, normal to low fibrinogen levels, circulating soluble fibrin and increasing amounts of FDP . Persistent extreme values were observed in 2 patients that died, whereas coagulation/fibrinolysis parameters frequently improved during plasmapheresis and gradually (more than 6 days) returned to normal values in the survivors . Although plasmapheresis was largely successful and signs of DIC and fibrinolysis were normalized, 2 patients died and 1 survived with severe sequelae . Thus, it remains to accumulate more data to conclude if plasmapheresis is beneficial in the treatment of severe septic shock and DIC.

Arkh Patol, 1985, 47(8), 26 - 32
{Pathogenetic and pathomorphological problems of viral-bacterial associations in children dying of meningococcal infection}; Tsinzerling VA et al.; The information on 63 children dying from hypertoxic forms of meningococcal infection is presented . Four groups of brain damage by respiratory viruses (RV) are distinguished on the basis of the results of morphological and virological examination: 1) with a recent RV generalization (26 cases); 2) with dissemination of an etiological agent but without clear-cut structural changes (6 cases); 3) with an isolated affection of the brain (13 cases); 4) without clear-cut brain damage . Experimental influenza-meningococcal infection was reproduced in 260 white rats . Enhancement of the animal death rate, multiplication of virus and the degree of brain damage in cases of combined action of both etiological agents is demonstrated . The ability of influenza virus, when inoculated intranasally together with meningococcus, to penetrate and to multiply in the brain provoking meningitis and choroiditis is shown virologically, histologically and electron microscopically.

Eur Neurol, 1985, 24(5), 310 - 3
Peripheral neuropathy in meningococcal septicemia; Roig M et al.; We report a case of a mixed sensorimotor, predominantly axonal mononeuritis multiplex that developed after a severe meningococcal septicemia and disseminated intravascular coagulation (DIC) with associated distal limb necrosis . Ischemia resulting from the DIC-induced multiple vascular occlusions is suggested as the leading cause of this neuropathy.

Scand J Infect Dis, 1985, 17(1), 19 - 24
Restriction fingerprinting and serology in a small outbreak of B15 meningococcal disease among Norwegian soldiers; Kristiansen BE et al.; In September 1981 a soldier died from meningococcal septicemia in a military camp in Mid-Norway . Soon afterwards one of his room-mates was transferred to a military camp in Northern-Norway where he shared sleeping quarters (room 7D) with 5 other soldiers of whom 2 fell ill with meningococcal disease 1 month later . Throat cultures were obtained from all 128 soldiers at the military camp in Northern-Norway; 41 (32%) harboured meningococci in their throats . The 3 invasive isolates and the isolates from the 4 healthy carriers at room 7D were all group B and type 15 meningococci . However, by DNA fingerprinting we could identify at least 2, probably 3, different individual strains among these 7 isolates . None of these strains were isolated from soldiers outside room 7D . By use of a B15 whole-bacterium ELISA method we showed that the levels of antimeningococcal IgG antibodies in the sera of the two cases at room 7D were low (18 and 28 OD units) compared with the mean IgG levels in the sera of their 4 healthy room mates (1150 OD units) and the mean IgG in the sera from all healthy soldiers (472 OD units).

Int J Tissue React, 1985, 7(4), 321 - 8
The clinical significance of alpha 1-antitrypsin-elastase (alpha 1AT-ELP) and alpha 2-antiplasmin-plasmin (alpha 2AP-PL) complexes for the differentiation of coagulation protein turnover: indications for plasma protein substitution in patients with septicaemia; Seitz R et al.; In inflammation, particularly in septicaemia, complex coagulation disorders may lead to a dangerous haemorrhagic diathesis . The conventional concept for this syndrome called DIC implicates the occurrence of active thrombin in the circulation, which may be followed by hyperfibrinolysis due to plasmin formation . In this study data are presented suggesting an important role for a third proteolytic system, granulocytic elastase . The complexes of plasmin and elastase with their specific inhibitors, alpha 2-antiplasmin-plasmin (alpha 2AP-PI) and alpha 1-antitrypsin-elastase (alpha 1AT-ELP) were determined immunologically . The alpha 1AT-ELP appears mainly in gram-negative septicaemia, particularly in meningococcal disease . The estimation of alpha 2AP-PI and alpha 1AT-ELP, together with a method for the detection of the antithrombin III--thrombin complex which remains to be established, is a suitable tool for for the differential diagnosis of the consumption of coagulation proteins . The assumption that at least three proteolytic systems participate in the development of the haemorrhagic diathesis during inflammation leads to the concept of a broad, comprehensive substitution therapy with e.g . concentrates of AT III, PPSB, or fresh frozen plasma . The aim of this treatment is to replace not only the consumed procoagulatory factors, but also the lacking inhibitors in order to control this "abnormal proteolysis syndrome".

Dev Biol Stand, 1985, 61, 525 - 30
A semi-synthetic glycoconjugate antigen prepared by chemical glycosilation of pertussis toxin by a meningococcal group C oligosaccharide hapten; Porro M et al.; The preparation of a hybrid molecule obtained by chemical glycosilation of pertussis toxin (PT) is reported, with the purpose of obtaining a semi-synthetic glycoprotein antigen with bivalent antigenicity . The chemical glycosilation was performed using an oligosaccharide hapten derived from the purified capsular polysaccharide of Neisseria meningitidis group C . The semi-synthetic molecule was investigated by chemico-physical and immunochemical analysis . The oligosaccharide haptens appeared exposed on the surface of the carrier protein PT, since the glycoprotein inhibited the immunoprecipitate between a specific polyclonal antiserum and the native bacterial capsular polysaccharide . By contrast, the main antigenic regions recognized in the native protein PT by specific polyclonal antibodies appeared lost after the coupling procedure involving PT as the carrier protein.

N Z Med J, 1984 Dec 12, 97(769), 860 - 2
An outbreak of meningococcal disease: implications for community medicine; Buchan H et al.; A local outbreak of five hospitalised cases of meningococcal disease, one of which was fatal, occurred over a period of three weeks in a small community in one health district . The events surrounding this outbreak illustrate many of the problems of dealing with the community medicine aspects of potentially serious infectious disease . Difficulties in the management of the outbreak are identified and contributing factors discussed.

NIPH Ann, 1984 Dec, 7(2), 69 - 82
Late sequelae after meningococcal disease as related to anamnestic and clinical factors recorded during the acute illness; Sander J et al.; In 71 males who survived acute meningococcal disease 3 to 15 years ago at an age of about 20, associations between acute clinical conditions (including a few pre- and post-admission variables) and late sequelae have been studied . There was a higher rate of sequelae symptoms (mainly light neurological and mental disturbances) among survivors from meningitis (76%) than among those who had had both meningitis and septicemia (58%) or pure septicemia (50%) . Twenty percent of control persons experienced such symptoms . "Changed Life" because of serious educational and working problems followed in 29% of the meningitis cases and 70% of the septicemia cases . Most of the clinical and laboratory factors separately examined were not significantly correlated to the sequelae rates . However, less than 2.5 mmol/l glucose in the cerebrospinal fluid (CSF) on admission (p less than 0.01), more than 1000 X 10(6) white blood cells per 1 in the cerebrospinal fluid (p less than 0.05), fever for more than 8 days (p less than 0.05), and probable cerebral symptoms the first week (p less than 0.05), were all positively correlated to a high rate of late sequelae . Well documented early sequelae correlated with serious late sequelae (p = 0.05) . No conspicuous associations between acute antibiotic treatment and late sequelae were found . A combination of CSF glucose, blood thrombocytes, and cells in CSF on admission yielded a multiple regression score which seems to be a moderately reliable predictor of sequelae (R = 0.46) . Hospital treatment should both aim at avoiding death and escaping residual effects . Because many prognostic factors for sequelae on admission are different from those for lethality, scoring for sequelae may be helpful in such secondary prevention of sequelae . Early standardized registration of sequelae may also be of value in tertiary prevention.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Dec, (12), 83 - 8
{Immunohormonal homeostasis in meningococcal meningitis}; Sokolov IaA et al.; The examination of 18 patients with meningococcal infection has revealed the presence of reciprocal relationships between changes in the content of cortisol and triiodothyronine in their blood, especially at the beginning of the disease . The dynamics of changes in the concentration of rosette-forming cells has proved to be similar to that of changes in the concentration of triiodothyronine . A decrease in the level of thyroid hormones in the blood has been observed in experimental infections and oncological processes in mice, rats or guinea pigs, as well as after the injection of adjuvants into these animals . The centroid factor analysis with the use of the criteria of symmetry and asymmetry has revealed 3 main factors in the process under study, interpreted as follows: the homeostasis destabilization factor of infectious nature (F1), the homeostasis maintenance and restoration factor of endogenous nature (F2) and the factor of the integral relationship catabolism/anabolism between energy streams in the body (F3).

South Med J, 1984 Dec, 77(12), 1610 - 1
Primary meningococcal arthritis; Siebert WT et al.; We have reported a case of primary meningococcal arthritis of the left ankle in a previously healthy man . Although primary meningococcal arthritis clinically resembles gonococcal arthritis, prolonged antibiotic therapy and open joint drainage are often required . Even with prompt appropriate antibiotic and surgical therapy, primary meningococcal arthritis may lead to permanent joint damage.

NIPH Ann, 1984 Dec, 7(2), 47 - 59
The virulence in mice of Neisseria meningitidis variants differing in free endotoxin activities and cell envelope properties; Andersen BM et al.; The virulence of two serogroup B meningococcal strains (270E+ and 840E+) having a high endotoxin release during in vitro growth, was compared with the virulence of corresponding variants (270E- and 840E-) liberating less endotoxin . The E-variants were isolated during subcultivations from the E+ strains . 270E+ and 840E+ were both serotype 15:P1.16, while 270E- was serotype 15:P1.2 and 840E- was non-typable . The SDS-PAGE patterns of the E+ and E- variants were also dissimilar . The E+ and E- variants differed in several other properties . Groups of mice were inoculated intravenously (i.v.) or intraperitoneally (i.p.) with E+ and E- meningococci . The endotoxin activities of inoculates and mouse blood were assayed by a Limulus lysate test . The mice received a similar infective dose of E+ and E- variants . A higher level of CFU and endotoxin was found in heart blood of E+ than of E-infected mice during the first hours after infection . Both 30h and 72h after inoculation, E+ variants were significantly more lethal to mice than E- variants (p less than 0.01).

Carbohydr Res, 1984 Dec 1, 134(2), 229 - 43
Rate, mechanism, and immunochemical studies of lactonisation in serogroup B and C polysaccharides of Neisseria meningitidis; Lifely MR et al.; Meningococcal Serogroup B polysaccharide and colominic acid, which are (2----8)-alpha-linked homopolymers of sialic acid, undergo lactonisation at low pH at a rate which is dependent upon the molecular size and upon the salt form (Na+ or Ca2+) . Meningococcal Serogroup C polysaccharide, a (2----9)-alpha-linked homopolymer of sialic acid with acetyl groups present at O-7 and/or O-8, reacts with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide to give an O-acylisourea . The rate of formation of O-acylisourea does not differ substantially between O-acetylated (O-Ac+) C, non-O-acetylated (O-Ac-) C, and B polysaccharide . 13C-N.m.r . spectroscopy shows that, in the absence of O-acetyl groups, the majority of the activated carboxyl groups of C polysaccharide condense with an adjacent HO-8 to form a delta-lactone . Immunochemical studies show that the antigenicity of B polysaccharide is markedly reduced on lactonisation of less than 20%, as measured by a radioimmunoassay using an anti-B monoclonal antibody, and that low-molecular-weight colominic acid is poorly antigenic both before and after lactonisation, suggesting the presence of conformational determinants on B polysaccharide . In contrast, lactonisation and/or formation of O-acylisourea groups in the (O-Ac+)-C polysaccharide does not cause a significant decrease in the antigenicity, which is consistent with a sequential (structural) determinant on the molecule.

Can J Microbiol, 1984 Dec, 30(12), 1453 - 7
Sulphur acquisition by Neisseria meningitidis; Port JL et al.; Group B Neisseria meningitidis (SD1C) was grown on defined medium supplemented with each of a variety of sulphur compounds as the sole source of sulphur . The organism grew on sulphate, sulphite, bisulphite, thiosulphate, dithionite, hydrosulphide, thiocyanate, L-cysteine, L-cystine, reduced glutathione, methionine, mercaptosuccinate, and lanthionine, but not on dithionate unless previously sulphur starved . Good growth was seen on concentrations of sulphate or thiosulphate as low as 10 microM . When pregrown on and subsequently starved for sulphate, the meningococcus showed enhanced transport capacity for this ion . Optimal conditions for assessing sulphur transport by active sulphur-limited cells were determined . The maximal sulphate uptake velocity was 9.3 nmol sulphate X mg protein-1 X min-1, and the apparent Km was 1.4 microM, far below human nasopharyngeal or serum sulphate levels.

Br J Vener Dis, 1984 Dec, 60(6), 380 - 3
Comparison between bacampicillin and amoxycillin in treating genital and extragenital infection with Neisseria gonorrhoeae and pharyngeal infection with Neisseria meningitidis; Edwards LD et al.; Sixty three patients presumed to have genital gonorrhoea who gave histories of extragenital sexual practices were randomly treated with amoxycillin 3 g or bacampicillin 4.8 g (equivalent to 3.5 g ampicillin) with probenecid 1 g to compare the efficacy of the drugs in treating gonorrhoea at all sites . Three patients were initially culture negative, and seven failed to return for follow up . Twenty seven of 28 patients receiving bacampicillin and all 25 receiving amoxycillin gave negative genital cultures for Neisseria gonorrhoeae five to nine days after treatment . Twenty two of 60 patients had extragenital gonorrhoea . One failed to return, but all eight who had received amoxycillin and 12 of 13 who had received bacampicillin gave negative pharyngeal and anorectal cultures after treatment . N meningitidis was isolated from the pharynx in 17 of 60 patients on initial attendance . Three of 14 were still colonised with the meningococcus after treatment . Two of 32 patients receiving amoxycillin and 12 of 31 receiving bacampicillin reported experiencing gastrointestinal side effects.

Crit Care Med, 1984 Dec, 12(12), 1021 - 3
Myocardial depression in septic shock caused by meningococcal infection; Monsalve F et al.; Comparative hemodynamic measurements recorded in 19 cases of septic shock associated with Neisseria meningitidis bacteremia and in 20 shock cases associated with bacteremia due to other Gram-negative bacilli showed a significantly higher incidence of early myocardial depression in the cases with meningococcal infection . Echocardiographic, ECG, and serum enzyme (CK-MB isoenzyme) studies closely correlated with impaired myocardial contractility and development of cardiogenic shock in patients with meningococcal bacteremia . Autopsy of the heart from three patients who succumbed to shock confirmed the presence of myocarditis with intracellular Gram-negative diplococci . Our observations suggest that the onset of cardiac dysfunction precedes clinical manifestations of shock.

Infect Immun, 1984 Dec, 46(3), 673 - 6
Human opsonins to meningococci after vaccination; Halstensen A et al.; Two groups of volunteers were immunized with either a serogroup A plus C meningococcal polysaccharide vaccine or a combined serogroup B polysaccharide-serotype 2 protein vaccine . Serum opsonin responses were measured by chemiluminescence of polymorphonuclear leukocytes exposed to opsonized live meningococci . Two of the six volunteers immunized with the A plus C vaccine had an increase in serum opsonins to group A meningococci, four responded to group C meningococci, and none to group B meningococci . Five other volunteers who were immunized with the combined group B polysaccharide-serotype 2 protein vaccine responded with an increase in serum opsonins to group B meningococci of two different protein serotypes, as well as to a group C-serotype 2 meningococcal strain . Although no booster effect was observed after a second dose of the combined vaccine, both the polysaccharide and the protein components appear to be able to stimulate an opsonin response.

S Afr Med J, 1984 Nov 17, 66(20), 759 - 62
Meningitis in Cape Town children; Potter PC et al.; A prospective clinical and microbiological survey of 213 children who presented to the teaching hospitals of the Cape Peninsula with meningitis was performed during a winter month . The predominant bacterium isolated was Neisseria meningitidis and this survey uncovered an outbreak of viral meningitis due to echovirus 4 of the Du Toit strain . In comparison with previous studies, the absence of fever in 20% of the cases of meningococcal disease and the isolation of N . meningitidis group B organisms which were resistant to sulphonamides are noted . Cases of N . meningitidis meningitis with initial clinical and cerebrospinal fluid findings indistinguishable from those in echovirus 4 meningitis are presented to emphasize the difficulties encountered in making a differential diagnosis . We recommend that in endemic areas all children with meningitis should be observed in hospital for at least 48 hours until the diagnosis of N . meningitidis has been excluded bacteriologically.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Nov, (11), 88 - 92
{Evaluation of the reactogenic and immunogenic properties of meningococcal vaccines}; Demina AA et al.; The results of the study of the reactogenic and immunogenic properties of meningococcal polysaccharide A + C vaccine in the controlled epidemiological trial, with regard to variations depending on the initial immunological characteristics of vaccinees in terms of the levels of antibodies to the polysaccharides contained in the vaccine, are presented . The study was made on school children: 303 of them were immunized with the meningococcal vaccine under test, and 229 (controls) with adsorbed diphtheria-tetanus toxoid . This study revealed that the reactogenic properties of the preparation were more pronounced in those children whose blood sera had been found to contain no antibodies to polysaccharides A and C prior to immunization . The immunological properties were more pronounced with respect to polysaccharide A . The titer of antibodies to polysaccharide A was found to depend on the previous immunological status of the child, which was indicative of the booster effect produced by the vaccine . The data obtained in the study suggest that the evaluation of the reactogenic and immunogenic properties of newly developed prophylactic preparations should be made with due regard for the previous immunological status of vaccinees in respect to the antigens contained in the meningococcal vaccine under test.

Pediatr Infect Dis, 1984 Nov-Dec, 3(6), 523 - 5
Meningococcal group Y disease in children; Stephens DS et al.; Neisseria meningitidis Group Y has been considered to be an uncommon pathogen in children . We reviewed the cases of Group Y meningococcal disease in children managed at our institution from 1974 through 1982 . Twenty-four percent (6 of 25 cases) of the meningococcal disease in children between 5 and 20 years of age was caused by N . meningitidis Group Y . This serogroup of meningococcus was not isolated from children younger than 5 years of age . Meningococcemia characterized by purpura fulminans was the most common presentation . Pneumonia, a common presentation of Group Y meningococcal disease in military recruits, was not observed . Group Y meningococcal disease had emerged as a cause of meningococcemia and meningitis in older children and adolescents.

Infect Immun, 1984 Nov, 46(2), 489 - 94
Inflammation triggers hypoferremia and de novo synthesis of serum transferrin and ceruloplasmin in mice; Beaumier DL et al.; Oil of turpentine was used to induce an artificial inflammation so that we could study its effect on iron metabolism and on synthesis of serum transferrin and ceruloplasmin in mice . It was found that turpentine-induced inflammation triggered the establishment of a hypoferremic state characterized by low levels of serum iron, followed by recovery and a gradual return to normal plasma iron levels . This turpentine-induced hypoferremia and its subsequent recovery paralleled the hypoferremia obtained during meningococcal infection . Moreover, serum transferrin and ceruloplasmin activity levels increased drastically during the recovery from hypoferremia . {14C}leucine incorporation studies revealed a de novo synthesis of both transferrin and ceruloplasmin . Turpentine-induced hypoferremia was also found to provide a protective effect against meningococcal infection which could be partially reversed by exogenous iron . The results of this study suggest that transferrin and ceruloplasmin may be synthesized partly in response to the altered iron metabolism observed during hypoferremia.

Infect Immun, 1984 Nov, 46(2), 408 - 14
Development of a Neisseria meningitidis group B serotype 2b protein vaccine and evaluation in a mouse model; Wang LY et al.; Although serotype 2 remains the predominant cause of group B Neisseria meningitidis disease in many parts of the world, most cases of this disease are now due to serotype 2b rather than 2a . For this reason, we adapted the serotype 2a vaccine method of C . E . Frasch and M . S . Peppler (Infect . Immun . 37:271-280, 1982) to the production of a serotype 2b protein vaccine . A spontaneously occurring nonencapsulated mutant of the group B serotype 2b strain 3006 was obtained by selection on group B antiserum agar . Serotype 2b outer membrane protein vaccines were prepared with less than 1% lipoplysaccharide contamination . The immunogenicity of these vaccines was evaluated in mice in the presence and absence of meningococcal group B and group C capsular polysaccharides . The group B and group C polysaccharides equally potentiated the antibody response to the serotype 2b protein . Addition of aluminum hydroxide or aluminum phosphate markedly improved the antibody response to the serotype 2b protein, but aluminum hydroxide-adjuvanted vaccines consistently elicited higher antibody levels . Aluminum hydroxide-adsorbed serotype 2a and 2b protein vaccines were evaluated for induction of cross-protective bactericidal antibodies . The 2a vaccines were 2a specific, whereas the 2b vaccines elicited antibodies strongly bactericidal for both 2a and 2b meningococcal strains and protected against bacteremia in a mouse model . It may therefore be possible to provide protection against both 2a and 2b disease by using an aluminum hydroxide-adsorbed protein vaccine containing a single serotype 2 protein component.

Infect Immun, 1984 Nov, 46(2), 507 - 13
Loss of pili and decreased attachment to human cells by Neisseria meningitidis and Neisseria gonorrhoeae exposed to subinhibitory concentrations of antibiotics; Stephens DS et al.; Recent evidence has suggested that surface structures of pathogenic bacteria, which are important in attachment to human mucosal surfaces, may be absent on bacteria grown in the presence of subinhibitory concentrations of antibiotics . We studied the effect of tetracycline and penicillin on meningococcal and gonococcal pili . Subinhibitory concentrations of tetracycline and penicillin were found to markedly reduce the number of pili per meningococcus or gonococcus and the percentage of meningococci or gonococci with pili, as determined by negative-staining electron microscopy . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane preparations suggested that tetracycline decreased expression of pili by inhibiting synthesis of pilin subunits . In contrast, pilin subunit synthesis was unaltered by penicillin, suggesting a defect in assembly of pilin subunits or in anchoring of assembled pili . The decrease in the number of pili that occurred with subinhibitory concentrations of both tetracycline and penicillin was accompanied by a marked decrease in the ability of the organisms to attach to human cells . Gonococci or meningococci removed from the influence of subinhibitory concentrations of the antibiotics regained piliation, and attachment returned to levels near those of controls . The expression of meningococcal and gonococcal pili may be affected by factors that influence synthesis of pilin subunits or factors that interfere with the assembly and anchoring of pili in the outer membrane.

J Infect Dis, 1984 Nov, 150(5), 672 - 7
Differentiation of B15 strains of Neisseria meningitidis by DNA restriction endonuclease fingerprinting; Kristiansen BE et al.; The restriction endonuclease fingerprinting technique was applied to meningococcal DNA in an attempt to identify individual strains of Neisseria meningitidis B15 (serogroup B, serotype 15), which causes approximately 90% of cases of meningococcal disease in northern Norway . Thirty representative strains (10 each from asymptomatic pharyngeal carriers, patients with septicemia, and patients with meningitis) were investigated with the restriction endonucleases Hind III and Eco RI . The 10 carrier strains showed a remarkable heterogeneity of fingerprints that rendered each strain easily distinguishable from the others . The 10 strains from the blood and the 10 from the cerebrospinal fluid showed similar but not identical restriction patterns . The results obtained with the two endonucleases were in perfect agreement . Our data suggest that a large number of different B15 clones are present in the population of northern Norway, but that only one single clone causes invasive meningococcal disease.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Nov, (11), 60 - 5
{Cross-reacting intraspecies antigens of Neisseria meningitidis . II . The dynamics of antimeningococcal antibodies to cross-reacting antigens in different forms of meningococcal infection}; Martynov IuV et al.; The presence of antibodies to meningococci has been determined in the sera of 203 patients with meningococcal infection and 234 healthy persons by means of the indirect hemagglutination tests with the use of polyvalent erythrocyte diagnosticum . The tests have shown that antibodies to cross-reacting antigens can be detected both in patients with generalized forms of meningococcal infection and in healthy persons; the level and occurrence of these antibodies depend on the age of the subjects under examination and the form taken by the course of meningococcal infection . The study has revealed that the background level of antibodies to meningococci in healthy persons is mainly formed due to meningococcal carriership . Antibodies to cross-reacting meningococcal antigens have been shown to be capable of being transferred transplacentally.

Am J Med, 1984 Oct 19, 77(4C), 42 - 9
Rationale for clinical trials evaluating ceftriaxone in the therapy of bacterial meningitis; Scheld WM et al.; Ceftriaxone is a promising antimicrobial agent in the therapy of bacterial meningitis . The rationale for the clinical evaluation of ceftriaxone in patients with meningitis is based on the following favorable characteristics: ceftriaxone has excellent in vitro activity (MBC90 0.25 microgram/ml or less) against the major meningeal pathogens including meningococci, pneumococci, group B streptococci, Hemophilus influenzae, and Escherichia coli, but it is inactive against Listeria monocytogenes; ceftriaxone is rapidly bactericidal within purulent cerebrospinal fluid in experimental animal models of meningitis induced by pneumococci, group B streptococci, H . influenzae, and E . coli; against most of the major meningeal pathogens, the activity attained in cerebrospinal fluid in human subjects with bacterial meningitis is high (1:512 or greater) and active concentrations of ceftriaxone persist in cerebrospinal fluid for prolonged periods compared with those of other cephalosporins; the results of clinical trials reported to date in patients with meningitis are encouraging . Ceftriaxone deserves further clinical evaluation in the treatment of bacterial meningitis; the optimal dose, frequency of administration, and duration of therapy remain to be determined.

Postgrad Med J, 1984 Oct, 60(708), 668 - 9
Meningococcal meningitis presenting with bilateral deafness and ataxia; Sandyk R et al.; A 50-year-old man presented with bilateral deafness and ataxia of sudden onset and without constitutional symptoms or signs of meningeal irritation . He was subsequently proved to have meningococcal meningitis, and the deafness and ataxia resolved following appropriate antibiotic therapy.

J Pediatr, 1984 Oct, 105(4), 538 - 42
Myocardial dysfunction in children with acute meningococcemia; Boucek MM et al.; Acute meningococcemia is frequently associated with cardiovascular collapse of uncertain cause . Review of the records of 12 consecutive children revealed clinical evidence of myocardial dysfunction in six (50%) . Subsequently myocardial function was prospectively assessed clinically and echocardiographically in 12 children . Seven (58%) of the 12 children had echocardiographic evidence of myocardial dysfunction as defined by a depressed left ventricular shortening fraction (LVSF) . The mean LVSF in these seven children was 0.25 +/- 0.03, as compared with the mean LVSF of 0.39 +/- 0.7 in the remaining children . The LVSF estimate of myocardial function strongly correlated with cardiac output as measured by standard thermodilution (r = 0.98, P less than 0.01) . Acute meningococcemia was not fatal in those children without evidence of myocardial dysfunction . In contrast, three of the seven children with evidence of myocardial dysfunction died . In four children, echocardiographic evidence of left ventricular dysfunction preceded cardiovascular collapse and clinical recognition of myocardial dysfunction . In children with an initially low LVSF, recovery of LVSF was associated with survival . Children with acute meningococcemia may have impaired myocardial function as indicated by depressed LVSF, resulting in low cardiac output despite normal intravascular volume . Thus, in addition to restoring intravascular volume, knowledge of the status of myocardial function may help direct therapy toward optimizing myocardial contractility.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Oct, (10), 27 - 30
{Determination of meningococcal antibodies by a radial hemolysis method}; Martynov IuV et al.; The possibility of using, on principle, the reaction of radial hemolysis for the determination of antibodies to meningococci has been shown . The sensitivity and resolution of this method has been found to depend on the dose of the antigen used for the sensitization of erythrocytes, on the concentration of the erythrocyte suspension introduced into the gel and on the amount of complement . The optimum conditions for the reaction of optimum hemolysis, used for the determination of antibodies to serogroup A Neisseria meningitidis polysaccharide, have been established: the sensitizing dose of the antigen must be 50-100 micrograms/ml, the concentration of sensitized erythrocytes 25%, and the amount of complement 20-40 HU.

Sex Transm Dis, 1984 Oct-Dec, 11(4), 296 - 300
In vitro inhibition of growth of Neisseria gonorrhoeae by Neisseria meningitidis isolated from the pharynx of homosexual men; Bisaillon JG et al.; Despite the high prevalence of pharyngeal gonorrhea and of meningococcal carriage among homosexual men, Neisseria gonorrhoeae and Neisseria meningitidis are rarely co-isolated from the throat . Forty-seven meningococcal isolates from the pharynx of homosexual men were examined, by a lawn-spotting method, for their ability to inhibit N . gonorrhoeae in vitro . Eight (17%) of the meningococcal isolates were inhibitory when tested against gonococci from the same patient, while 31 (66%) were inhibitory when tested against N . gonorrhoeae strain 650 (T1) . The colonial type T1 of a given strain was, in all cases tested, more sensitive to the inhibitory activities than the corresponding T4 type . Since the meningococci co-isolated from the throat with gonococci were at least as inhibitory in vitro as those isolated without gonococci, the natural resistance to gonococcal pharyngitis cannot be explained on the basis of the inhibitory activities produced by the meningococci in vitro . The inhibitory strains of N . meningitidis were identified in decreasing importance as: nonserogroupable, W135, C, B, 29E, and X . The addition of trypsin to the solid medium removed the inhibition produced by the meningococci, an observation suggesting the involvement of protein inhibitors.

Acta Pathol Microbiol Immunol Scand {C}, 1984 Oct, 92(5), 247 - 54
Affinity chromatography for purification of antibodies to Neisseria gonorrhoeae and Neisseria meningitidis lipopolysaccharides; Rodahl E et al.; Lipopolysaccharides (LPSs) were prepared by phenol-water extraction of the gonococcal strain 8551 and the group B meningococcal strain 44/76, digested with pronase, and purified by ultracentrifugation and Sepharose CL-6B fractionation in the presence of 1.5 per cent sodium deoxycholate . On SDS-PAGE with 10 per cent acrylamide the purified 125I-labelled LPSs migrated as single, low-molecular-weight components . The LPSs were coupled to CNBr-activated Sepharose 4B for affinity purification of antibodies to the common antigenic factor 1 and the sero-type factor 5 of LPS 8551, and antibodies to LPS 44/76 . The antibodies eluted showed ELISA activity against wells coated with LPS or whole cells of the bacteria, the antibody activity being inhibited by LPS . SDS-PAGE of whole cells of the strain 8551 and immunoblotting with the anti-factor 1 or -factor 5 antibodies resulted in single, broad bands corresponding to the low-molecular-weight LPS subunits.

Can J Microbiol, 1984 Oct, 30(10), 1289 - 91
Serotype distribution of meningococci isolated in South Australia 1971 through 1980; Ashton FE et al.; The serotypes of meningococci isolated from 76 sporadic cases of meningococcal disease in South Australia during the years 1971 through 1980 were determined . Thirty-four (56%) of the 61 group B strains were nontypable; the remainder were of five serotypes namely 8 (16%), 1 (13%), 2 (2a and 2b) (9%), 12 (3%), and 15 (3%) . Four of the five group B type 2 strains were serotype 2b . Serotype 2a accounted for four of seven group C strains and four of five group W135 strains . Overall serotypes 2 (2a and 2b) (17%), 8 (13%), and 1 (10%) occurred most frequently amongst the typable strains, whereas 40 (53%) of the 76 strains were nontypable . The results indicate that several serotypes and many nontypable strains were responsible for the sporadic disease occurring during a 10-year period in Australia.

J Hyg (Lond), 1984 Oct, 93(2), 167 - 80
Meningococcal infections in Scotland 1972-82; Fallon RJ et al.; Strains of Neisseria meningitidis isolated from patients with meningitis or septicaemia without meningitis in Scotland during the years 1972-82 have been reviewed together with details of the age, sex, disease and outcome of the patients from whom they were isolated . A total of 1185 strains were isolated, of which 927 were examined at the Meningococcal Reference Laboratory (Scotland): 19.3% were of serogroup A, 63% of group B, 9.6% of group C, 6% of W135 and 1.6% of other groups . Non-groupable strains were rare . Disease was most common in the first years of life but there was a difference in the age distribution of disease due to the different serogroups, the proportion of disease due to group B being smaller in adults than that due to other serogroups . The overall mortality in meningitis was 7.5% and in septicaemia was 20.6%, although there were differences between the rates for the various serogroups . The serogroup distribution differed in disease as opposed to meningococci isolated from carriers although group B strains were predominant in both series . Overall, approximately 15% of strains were resistant to sulphadiazine, the proportion of resistant group A strains being higher than that of other serogroups.

Eur J Clin Microbiol, 1984 Oct, 3(5), 439 - 41
Magnitude of bacteremia and complement activation during Neisseria meningitidis infection: study of two co-primary cases with different clinical presentations; Zwahlen A et al.; Two co-primary cases of schoolchildren with acute meningococcal disease due to infection with Neisseria meningitidis serogroup B are described . The first patient presented with septic shock and purpura fulminans, bacteremia greater than 10(5) organisms/ml blood, low C3 and factor B levels and an elevated level of C3d . The second patient had meningitis, negative blood cultures, normal levels of serum complement components but more than 10(4) organisms/ml in CSF . A comparison of the quantitative bacteriology data and complement profiles for these patients suggests that the degree of activation of complement during meningococcemia is directly related to the number of organisms in the blood . This association may determine the different clinical syndromes.

J Clin Pathol, 1984 Oct, 37(10), 1123 - 8
Plasmids in throat and genital isolates of meningococci; Ison CA et al.; Plasmids 1.6, 2.8, or greater than 40 megadaltons in size were found in one urethral and nine throat strains of meningococci . Throat meningococci are known to be heterogeneous in their aminopeptidase profiles . Their unexpected content of plasmids is further evidence of their difference from classic systemic strains . Although the 2.8 megadalton plasmid has some resemblance to the well known 2.6 megadalton gonococcal plasmid, restriction enzyme studies gave no evidence of identity . Possible sources of the plasmids are discussed.

J Clin Microbiol, 1984 Oct, 20(4), 672 - 6
Comparison of radioimmunoassay and enzyme-linked immunosorbent assay in measurement of antibodies to Neisseria meningitidis group A capsular polysaccharide; Beuvery EC et al.; Antibodies to meningococcal group A polysaccharide were determined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) in serum samples from 16 adults vaccinated with bivalent meningococcal group A and C polysaccharide vaccine . The specific antibody levels in the serum samples were expressed as micrograms of antibody protein per milliliter of serum . For RIA the polysaccharide was radiolabeled extrinsically with 125I . Both native polysaccharide and polysaccharide labeled with 127I were used in ELISA . Because these antigens gave similar results, it can be concluded that the introduction of tyramine and iodine by the labeling procedure did not alter the antigenic activity of the polysaccharide . The reproducibility of RIA was clearly better than that of ELISA . The antibody levels detected by the methods were equal, which means that ELISA can be used satisfactorily to measure antibodies to meningococcal group A polysaccharide quantitatively . Some discrepant results were found due to an underestimation of immunoglobulin M antibodies in ELISA . This was shown by a correlation test in which a weakly significant negative correlation was found between the immunoglobulin M antibody level/immunoglobulin G antibody level ratio and the RIA antibody level/ELISA antibody level ratio.

South Med J, 1984 Oct, 77(10), 1234 - 9
Meningococcal meningitis in children: clinical comparison of disease produced by the minor and major serologic groups of Neisseria meningitidis; Ryan NJ et al.; Since 1972, there has been an increased incidence of meningococcal disease due to the minor serologic groups, "serogroups," of Neisseria meningitidis . Few cases, however, have been reported in pediatric patients . We present 24 cases of meningococcal meningitis, ten of them (42%) due to serogroups X, Y, and Z N meningitidis . We believe these cases to be the largest group of pediatric patients with such meningitis thus far reported . The clinical disease produced by the minor serogroups was indistinguishable from that produced by the major serogroups . Our experience supports previous published reports that severe meningococcal disease does occur with the minor serogroups of N meningitidis, and this increasing incidence may be of major importance if vaccination programs are to be effective in controlling epidemic meningococcal disease.

Infect Immun, 1984 Oct, 46(1), 260 - 6
Monoclonal antibodies to serotype 2 and serotype 15 outer membrane proteins of Neisseria meningitidis and their use in serotyping; Zollinger WD et al.; A series of murine monoclonal antibodies to serotype 2 and serotype 15 strains of Neisseria meningitidis were produced which were specific for outer membrane proteins of classes 1, 2, 3, and 5 . A panel of eight monoclonal antibodies that exhibited a high degree of serotype specificity when reacted with prototype strains of known serotype were selected for study . Each of the corresponding epitopes was localized on a specific outer membrane protein by means of immunoprecipitation, electroblotting, or both . The serotype 2a-, 2b-, and 2c-specific antibodies bound to the class 2 protein, the serotype 15-specific antibody bound to the class 3 protein, two antibodies (3-1-P1.2 and 3-1-P1.16) bound to class 1 proteins, and two antibodies (1-1-P5.1 and 3-1-P5.2) bound to class 5 proteins . Six of these monoclonal antibodies were used in a spot-blot procedure to survey 122 case isolates (groups B, C, Y, and W135) and 363 carrier isolates (all serogroups) for the presence of the 2a, 2b, 2c, 15, P1.2, and P1.16 epitopes . A total of 66% of the case isolates and 30% of the carrier isolates reacted with one or more of the monoclonal antibodies . The use of monoclonal antibodies for serotyping of meningococci appears to be feasible and easy and appears to have significant advantages over the use of polyclonal typing sera.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Oct, (10), 99 - 102
{Immunoepidemiological characteristics of the duration of a meningococcal carrier state}; Deviatkina NP et al.; 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.

An Esp Pediatr, 1984 Sep 15, 21(3), 229 - 37
{Bacterial meningitis in children . Analysis of 181 cases}; Roman Pinana JM et al.; Clinical records of 181 children, aged between one month and seven years, admitted in a four year period, from 1978 through 1982, with the diagnosis of bacterial meningitis are revised . Peak incidence occurred in the age group between six months and three years, and during the months of January to May . N . meningitidis (35%), pneumococcus (4.9%) and H . influenzae (2.7%) were the most frequently isolated bacteria . CSF culture was negative in 56% of the children . All of them had previously taken antibiotics . Complications were present in 6.4%, with highest incidence in the known-agent group, on the following order: septic shock, 11%, seizures, 6.6%, and subdural effusion, 2.2% . Permanent sequelae were present in 3.8%, being deafness predominant . Twelve (6.3%) out of the 181 died, and death was result of fulminant meningococcal sepsis with endotoxic shock in ten of these patients . Clinical and psychological followed-up of twenty-nine children with isolated causal agent, were compared with a control group, finding no statistically-significant difference.

S Afr Med J, 1984 Sep 1, 66(9), 345 - 6
Recurrent meningococcal meningitis . A case report; Hardcastle SW; A 17-year-old Coloured youth presented at Tygerberg Hospital on six occasions between 1978 and 1981 . He was admitted three times for meningococcal meningitis and three times for a meningitic illness clinically suggestive thereof . He had been admitted twice before to the City Hospital, Cape Town, in 1966 and 1968, for presumed meningococcal meningitis . He was fully evaluated in the outpatient department and found to have no detectable total haemolytic complement activity . There was no evidence of classic or alternative pathway activation . He has been tentatively designated as having a deficiency in the C6 or C8 components of the terminal membrane attack mechanism of the complement cascade.

Rev Infect Dis, 1984 Sep-Oct, 6(5), 625 - 32
Primary meningococcal pericarditis: a disease of adults associated with serogroup C Neisseria meningitidis; Blaser MJ et al.; Pericarditis due to Neisseria meningitidis is usually a consequence of meningeal disease or meningococcemia . This presentation includes a case report of primary meningococcal pericarditis (PMP) and a review of the clinical and epidemiologic features of 15 previously reported cases . All cases have been reported in the past 15 years . Most patients were older teenagers or adults . The median age and age distribution of PMP cases in the United States were significantly greater than that of patients with other meningococcal diseases reported to the Centers for Disease Control (CDC) (P = .005) . Similarly, serogroup C N . meningitidis was isolated from 88% of U.S . patients with PMP, compared with isolation from 22% of patients with other meningococcal diseases reported to the CDC (P = .00016) . Culture of pericardial fluid usually yielded meningococci, and most patients presented with signs and symptoms typical of purulent pericarditis . A positive pericardial culture was associated with the development of cardiac tamponade (P = .03) . With appropriate antibiotic treatment and drainage of pericardial fluid when indicated, all 16 patients survived and experienced few or no sequelae.

J Infect, 1984 Sep, 9(2), 197 - 202
Control of epidemic meningococcal meningitis by mass vaccination . II . Persistence of antibody four years after vaccination; Mohammed I et al.; Meningococcal antibody was measured in 928 persons vaccinated with combined groups A and C polysaccharide antigens in Bauchi State, Nigeria between 1979 and 1982 . Protective amounts of antibody were detected by the indirect haemagglutination technique up to 4 years after vaccination . This persistence was observed mainly in adults, although a substantial proportion of older children also had persistent antibody . Titres in younger children fell progressively, and by the third year the mean log2 antibody titre was 1.4; this may not confer protection against disease . A rational policy for vaccination against meningococcal meningitis would be to revaccinate younger children after 2 years, older children after 4 years, and adults after 6-8 or more years.

J Infect, 1984 Sep, 9(2), 190 - 6
Control of epidemic meningococcal meningitis by mass vaccination . I . Further epidemiological evaluation of groups A and C vaccines in northern Nigeria; Mohammed I et al.; PIP: In mass vaccination campaigns organized by several state governments in northern Nigeria in 1978-81, a total of 7,535,350 people received bivalent groups A and C polysaccharide meningitis vaccines in the states of Bauchi, Borno, Gongola, and Plateau . This figure represents 53% of the population of these 4 states, which are part of the African meningitis belt . Of the total number of reported cases of meningitis from the 4 states in the 1978-81 period, 5565 (80%) occurred in 1978 . As more persons were vaccinated over the years, the number of reported cases declined significantly in all states but Gongola, where the percentage vaccinated (19%) was lowest . By 1980 in Bauchi, where 78% of the population had been vaccinated, there were only 12 reported cases of meningitis and no deaths, and there has not been a single reported case of the disease in this state since 1981 . These findings confirm the effectiveness of mass vaccination in limiting meningococcal infection . Moreover, mass vaccination has the potential of eradicating the disease, unlike selective vaccination . Epidemiologic research suggests it may be necessary to undertake mass vaccination campaigns only among those 3-15 years of age once every 4-5 years .

J Infect, 1984 Sep, 9(2), 185 - 9
Validity of the recording of meningococcal disease according to various sources of information; De Wals P et al.; A study was made in Belgium in order to assess the completeness and specificity of the recording of meningococcal disease by routine sources of information . Ninety-three cases identified in a hospital survey were linked with those recorded in mortality statistics, in the notification of communicable diseases, and by the National Reference Laboratory for meningococci . Statistics based on mortality data appeared to be of low validity . The overall completeness of recording was 44% for the notification of communicable disease, and 40% for the reference laboratory . When these two sources were used for surveillance, the completeness of case-finding increased to 56% . When the analysis was restricted to bacteriologically-confirmed cases, the completeness of recording was 62% for the notification system, 70% for the laboratory, and 84% for both sources . The surveillance of communicable diseases should rely on various sources of information . Laboratory data should be systematically used in order to improve both the completeness of recording and the specificity of case-ascertainment.

Medicine (Baltimore), 1984 Sep, 63(5), 243 - 73
Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency; Ross SC et al.; Inherited deficiencies of the complement proteins are rare in unselected populations . Examination of patients with the clinical correlates of complement deficiency (autoimmune disease and certain bacterial infections) shows the frequency of inherited complement deficiency to rise enormously (5.9% of patients with systemic lupus erythematosus, 10 to 25% of adults with sporadic meningococcal disease) . Autoimmune diseases of all types, but especially systemic lupus erythematosus, discoid lupus and glomerulonephritis, are seen in all categories of complement deficiency, most typically in those of the early classical pathway (C1, C4, C2) . Pneumococcal infections are characteristic of deficiencies of the early classical pathway, as well . Deficiencies of C3 are associated with severe disease including autoimmune phenomena, pneumococcal and neisserial infections . C3-deficient patients become ill substantially earlier in life . Infections with N . meningitidis and N . gonorrhoeae are most typical of the late component deficiencies, with over 40% of homozygotes affected . Despite the presence of this deficiency from birth and the peak age-specific incidence of meningococcal disease in the general population at ages 3-8 months, the median age of first infection in the late component-deficient patients is 17 years . Relapse of infection is ten times more common in these patients, and discrete recurrences are seen in 45% of affected individuals . An unusual and unexplained predilection for infection with serogroup Y N . meningitidis exists . Despite an immune deficiency, and problems with ascertainment bias, it appears that persons with late component complement deficiency enjoy less mortality than normals who contract meningococcal disease . Attempts to explain the pathogenesis of neisserial infection in late component deficiencies have focused on the concept that normally non-pathogenic serum-sensitive bacteria are etiologic in the absence of serum bactericidal activity . Data to support this concept remain to be developed and contrary data exist . A separate mechanism may predispose properdin-deficient patients to meningococcal infection, since they appear to develop fulminant infections with high mortality.

Infect Immun, 1984 Sep, 45(3), 544 - 9
Heterogeneity of molecular size and antigenic expression within lipooligosaccharides of individual strains of Neisseria gonorrhoeae and Neisseria meningitidis; Schneider H et al.; We determined the Mr of neisserial lipooligosaccharides (LOS) by using discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis, minimal loading concentrations, and Salmonella isogenic rough mutant LOS as Mr standards . Salmonella LOS were resolved into three components . The migration distance of each component was linearly related to its theoretical Mr (r = 0.99) . Neisserial LOS also contained multiple components whose calculated Mr ranged from 3,200 to 7,100 . The relative abundance of components and their MrS varied greatly among strains . Meningococcal LOS were composed almost exclusively of two closely migrating components; gonococcal LOS were more heterogeneous . LOS from a gonococcus selected for resistance to a Pseudomonas pyocin contained only a single component that was different from and of intermediate Mr among the three components of the parent strain . A monoclonal antibody directed against the meningococcal L8 LOS epitope was used to determine whether heterogeneity of antigen expression reflected Mr heterogeneity . Single components of the L8 meningococcal LOS and of the LOS of 3 of 19 gonococcal strains bound the monoclonal antibody . Gonococcal LOS components that expressed the L8 epitope were of a similar Mr (4,800) . Smaller components of these same LOS did not express the epitope.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Sep, (9), 32 - 7
{Cross-reacting intraspecific antigens of Neisseria meningitidis . I . The isolation, immunochemical and serological characteristics of the cross-reacting antigens of N . meningitidis serogroup A}; Gracheva AM et al.; New data on the cross-reacting antigen of N . meningitidis, serogroup A, are presented . A complex of antigens has been isolated by treatment with tryptone X-100, ethanol precipitation and the subsequent treatment with trichloroacetic acid . The immunological analysis of the isolated preparation has shown that the proteinaceous part of the biopolymer contains 7 polypeptide fragments; of these, one fragment with a molecular weight of 31000 daltons has been found to constitute 49, 15% of all polypeptide fragments . The evaluation of the serological properties of this preparation in the precipitation test and the passive hemagglutination test has revealed that the preparation contains various cross-reactive antigenic determinants . Polyvalent erythrocyte diagnosticum obtained on the basis of this preparation permits the detection of antibodies to meningococci irrespective of their serogroup.

Rev Infect Dis, 1984 Sep-Oct, 6(5), 640 - 8
Group A meningococcal disease in the U.S . Pacific Northwest: epidemiology, clinical features, and effect of a vaccination control program; Counts GW et al.; In 1975 an outbreak of group A meningococcal disease began in Seattle, Washington, and cases subsequently were recognized throughout the Pacific Northwest . Nearly one-half of the affected persons were Native Americans; two-thirds were alcohol abusers and/or habitues of skid road communities . In Seattle, group A meningococci colonized asymptomatic persons only if these individuals had contact with skid road (P = .006) . The epidemic strain may have spread from American Indians in Manitoba, Canada . Traditional migration routes connect the two populations; asymptomatic American Indians on reservations in Washington carried group A meningococci . Vaccination programs were undertaken in four cities but only after cases occurred . In Seattle, vaccination reached 80% of the target population and was associated with a significant decrease in incidence of the disease, but cases recurred after the program ended . The social habits of skid road communities, combined with the "case-triggering" approach to, and premature termination of, vaccination programs, may have resulted in 56% of regional cases occurring after the start of the vaccination program in Seattle.

J Infect Dis, 1984 Sep, 150(3), 436 - 49
Reexamination of the protective role of the capsular polysaccharide (Vi antigen) of Salmonella typhi; Robbins JD et al.; The role of the Vi antigen, the capsular polysaccharide of Salmonella typhi, in the pathogenesis of and immunity to typhoid fever remains the subject of controversy . Vi-positive S . typhi resist phagocytosis and the action of serum complement, both of which actions are initiated by antibodies to Vi antigen . Both the laboratory potency in mice and the clinical effectiveness of whole-cell vaccines were related to their content of immunogenic Vi antigen . A Vi polysaccharide used for immunizing humans against experimental challenge with S . typhi failed to prevent typhoid fever; experimental conditions used to prepare this ineffective Vi antigen were shown to denature it and to reduce its immunogenicity . Assay of serum antibodies to Vi antigen with purified Vi antigen is a reliable method for diagnosis of typhoid fever and asymptomatic carriage of S . typhi . Vi polysaccharides prepared by modern techniques passed the requirements for meningococcal polysaccharide vaccines and had approximately 13 times the protective activity in the mouse potency assay as did the US Standard 6A whole-cell typhoid vaccine.

S Afr Med J, 1984 Aug 25, 66(8), 308 - 9
Neisseria flavescens septicaemia with meningitis . A case report; Coovadia YM; A rare case of septicaemia with meningitis caused by Neisseria flavescens is reported . The clinical presentation and initial bacteriological findings were indistinguishable from those in meningococcal septicaemia with purpura . A review of the literature for N . flavescens infections revealed 15 other cases of meningitis and 1 of septicaemia . A plea is made for the full identification of all Neisseria isolated, especially those isolated from cerebrospinal fluid and blood cultures, so that closely related members of the family Neisseriaceae are not confused.

Can J Microbiol, 1984 Aug, 30(8), 1042 - 5
Experimental meningococcal infection in neonatal mice: differences in virulence between strains isolated from human cases and carriers; Salit IE et al.; The lack of availability of a suitable animal model has limited understanding of the pathophysiology of meningococcal disease . We have utilized a neonatal mouse model in which atraumatic intranasal inoculation of meningococci results in nasopharyngeal colonization and ultimately bacteremia . Using this model, we compared the virulence of seven encapsulated meningococcal carrier strains with eight meningococcal strains which were isolated from cerebrospinal fluid or blood of patients (disease strains) . Intraperitoneal (IP) iron dextran was given to some animals to enhance meningococcal virulence . After IP iron, carrier strains were still poorly invasive with rates of bacteremia ranging from 0 to 15% (mean = 3%), whereas disease-associated strains were significantly more invasive and caused bacteremia in 31-64% of animals (mean = 39%) . Without iron injections, nasopharyngeal colonization rates were similar (36 versus 30%, P greater than 0.1) for case and carrier strains . IP iron dextran significantly enhanced rates of colonization and bacteremia caused by the disease strains only . We have, therefore, shown that the relative virulence of meningococcal strains for humans is maintained in this experimental model.

Can J Microbiol, 1984 Aug, 30(8), 1022 - 9
Experimental meningococcal infection in neonatal animals: models for mucosal invasiveness; Salit IE et al.; 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.

J Clin Microbiol, 1984 Aug, 20(2), 255 - 8
Filter radioimmunoassay, a method for large-scale serotyping of Neisseria meningitidis; de Marie S et al.; A simple and rapid filter radioimmunoassay method can be used to serotype meningococcal strains on a large scale . The technique consists of simultaneous inoculation of 96 strains on nitrocellulose filters . The resulting colonies can be processed in situ, by extraction and fixation, incubation with antibodies and 125I-labeled protein A, and, finally, autoradiography . Processing many filters simultaneously, one person can serotype thousands of meningococci in a week . Multiple filters with identical strain patterns can be stored after the fixation step for future screening . The use of monoclonal antibodies is essential; polyclonal antisera, even after extensive absorption, were not specific in this assay . When results from filter radioimmunoassay and Ouchterlony microprecipitation were compared for the serotyping of 201 Neisseria meningitidis strains for serotypes 2a and 2b, filter radioimmunoassay was sufficiently sensitive and specific to be useful in mass screening.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Aug, (8), 72 - 6
{Comparative study of the sensitivity and specificity of dried and liquid meningococcal erythrocyte diagnostic agents A, C and Y in a controlled trial}; Nikitiuk NM et al.; The comparative study of the sensitivity and specificity of dried and liquid meningococcal erythrocyte diagnosticums A, C and Y has been carried out in the indirect hemagglutination test with the sera of persons immunized with different doses of dried chemical meningococcal (group A) polysaccharide vaccine and persons receiving placebo under the conditions of a controlled epidemiological trial . The possibility of using, on principle, both liquid (A, C) and dried (A, C, Y) preparations in clinico-epidemiological studies has been established . The continuation of the research work aimed at the improvement of meningococcal diagnosticums and, in particular, at the development of polyvalent preparations seems to be justified.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Aug, (8), 52 - 5
{Serotypes of meningococci isolated in the USSR and the Republic of Cuba}; Demina AA et al.; The results of serotyping of 101 meningococcal strains isolated in the Soviet Union and 23 strains isolated in the Republic of Cuba are presented . Typing within groups was carried out by Frasch's method in the double diffusion test in gel . For this purpose serotype antigens were prepared from each strain . These antigens were used in the test only after their purification by ultracentrifugation . In all cases the prevalence of serotype 2 was revealed . A great number of Cuban strains contained a wide spectrum of type antigens of both protein and lipopolysaccharide nature . Serotype antigen 15 occurred in meningococci isolated both in the USSR and in Cuba . In most cases type 15 occurred in combination with types 2 and 8 . The comparison of the results obtained in the serotyping of meningococci isolated in situations, nonepidemic (USSR) and epidemic (Cuba) for serogroup B, gives no grounds for considering type 2 as the "marker of virulence" . Probably, this problem will be solved by the differentiation of subtypes within type 2 . Attention should be paid to the serotype antigens of the lipopolysaccharide nature with a view to their epidemiological evaluation.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Aug, (8), 44 - 7
{Characteristics of nonpathogenic Neisseria and Branhamella catarrhalis based on cytopathogenicity}; Galeeva OP et al.; The study of the action of 12 Neisseria species belonging to 112 strains, 6 B . catarrhalis strains and 202 meningococcal strains on the culture of continuous cell line F1 (human amniotic cells) has revealed that nonpathogenic Neisseria are essentially weaker than meningococci in their pathogenicity (expressed in terms of CPD50) . Among nonpathogenic Neisseria highly cytopathogenic strains occur in 13.9% of cases, which gives grounds for considering them opportunistic bacteria . Sharply pronounced correlation between the adhesive and pathogenic properties of Neisseria has been observed . The cytopathogenic action of Neisseria is accompanied by the lesion of the chromosomal apparatus of mitotic infected cells.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Aug, (8), 110 - 4
{Specific immunological reactivity in generalized forms of meningococcal infection in children}; Korzhueva NA et al.; The characteristics of immune responsiveness were studied in 455 children aged 2 months to 14 years with the generalized forms of meningococcal infection . In children of all age groups an increase in the titers of antibodies to meningococci was revealed; this increase started from day 4 of the disease, reached its maximum at the end of week 3 or the beginning of week 4 and correlated with the severity of the disease and the age of the patients . A drop in the IgG level in the course of the disease and a rise in the IgM level by the end of week 2 were observed . A decrease in the content of T-lymphocytes at the acute period of the disease and an increase in the number of B-lymphocytes, especially by the end of week 2 of the disease, were established.

Arch Intern Med, 1984 Jul, 144(7), 1481 - 2
Recurrent Neisseria meningitidis bacteremia . Association with deficiency of the eighth component of complement (C8) in a Sephardic Jewish family; Zimran A et al.; A 24-year-old man had repeated episodes of meningococcal meningitis . Selective deficiency of the eighth component of complement (C8) was demonstrated in the patient, his twin brother, and in one of five siblings . As the parents were first cousins of normal phenotype, this pattern is suggestive of an autosomal recessive heredity . The present report brings the total number of patients given the diagnosis of C8 deficiency to 14, and calls attention to the existence of this condition in Jews of Sephardic (Mediterranean) origin.

Am J Clin Pathol, 1984 Jul, 82(1), 97 - 9
Evaluation of the Directigen and Phadebact agglutination tests; McGraw TP et al.; Comparison testing of the Directigen latex agglutination (LA) kit, the Phadebact coagglutination (COA) kit, and counter-immunoelectrophoresis (CIE) demonstrated that the commercial LA reagents were slightly more sensitive than the COA reagents for the detection of pneumococcal polysaccharide types 2, 4, 8, 9, 12, 19, 23, 25, 51, and 56, and meningococcal polysaccharide from Group C . The COA reagents were slightly more sensitive than the LA reagents for the detection of pneumococcal polysaccharide type 6A . The sensitivity of LA and COA reagents for the detection of Hemophilus influenzae type b capsular polysaccharide, pneumococcal polysaccharide types 1, 3, 14, and meningococcal Group A were equivalent . Purified meningococcal polysaccharides of Groups B, C, and W135 were detected uniformly by CIE but not with the COA reagent . The COA reagent reacted with antigen of Groups B, C, and W135 from broth culture but with less sensitivity than CIE . In general, CIE was the least sensitive method for detecting bacterial antigens . In addition, the commercial CIE antisera for H . influenzae type b, or meningococcal polysaccharides were susceptible to false-negative results due to antigen excess.

J Biol Stand, 1984 Jul, 12(3), 241 - 6
Molecular sizing of individual polysaccharides in polyvalent pneumococcal and meningococcal vaccines by column chromatography and immunoelectrophoresis; Scheers R et al.; We determined the molecular size of meningococcal and pneumococcal polysaccharides in final vaccines, using a combination of column chromatography and simple rocket immunoelectrophoresis . We found a good correlation between the distribution coefficients obtained with UV monitoring or ELISA and immunoelectrophoresis.

South Med J, 1984 Jul, 77(7), 824 - 6
Indolent meningococcal meningitis: a cautionary tale; Simon HB et al.; Bacterial meningitis is a medical emergency that is ordinarily rapidly progressive . We present three patients who had meningococcal meningitis with an indolent course . Symptoms were present from two days to four weeks before hospitalization . Cerebrospinal fluid cultures grew Neisseria meningitidis one to eight days before antibiotic therapy, yet all patients remained fully alert and clinically stable during this interval . All recovered after penicillin therapy . In the future earlier diagnosis should be facilitated by an awareness of differing manifestations of meningococcal meningitis, including benign CSF findings, intact sensorium, and an indolent progression . Immunologic studies will be required to clarify the pathogenesis of this syndrome.

J Clin Microbiol, 1984 Jul, 20(1), 1 - 4
Superoxol and amylase inhibition tests for distinguishing gonococcal and nongonococcal cultures growing on selective media; Arko RJ et al.; Two inexpensive screening tests were evaluated singly and in tandem for distinguishing Neisseria gonorrhoeae from other oxidase-positive microorganisms growing on selective gonococcal media . In tests of 728 cultures, including 460 N . gonorrhoeae, 4 Neisseria lactamica, 257 Neisseria meningitidis, and 7 Branhamella catarrhalis, both Superoxol (30% H2O2; J . T . Baker Chemical Co., Phillipsburg, N.J.) and amylase inhibition tests were 100% sensitive (positive) for 20-h cultures of N . gonorrhoeae . Singly, the Superoxol test was 92.7% specific for N . gonorrhoeae, compared with a specificity of 82.3% for the amylase inhibition test . By using tandem screening tests to distinguish gonococci, we achieved an overall specificity of 98.6% . Group A meningococci were the primary source of error in the Superoxol test, with 97% (37 of 38) strains producing gonococcal like reactions for catalase . From 5 to 20% of N . meningitidis serogroups X, Y, Z, and Z' and nontypable strains, as well as about 50% of B . catarrhalis and N . lactamica strains, were also strong catalase producers.

J Clin Microbiol, 1984 Jul, 20(1), 40 - 2
Neutralization of the inhibitory effect of sodium polyanetholesulfonate on Neisseria meningitidis in blood cultures processed with the Du Pont Isolator System; Scribner RK et al.; The inhibitory and bactericidal effects of sodium polyanetholesulfonate on Neisseria meningitidis were neutralized by blood lysis which occurs within the pediatric Isolator 1.5 Microbial tube (E . I . du Pont de Nemours & Co., Inc., Wilmington, Del.) . Lysed blood was more effective than 2.5% gelatin in preventing the inhibitory effect . All but 1 of 16 N . meningitidis strains were killed by 0.06% sodium polyanetholesulfonate in the absence of lysed blood, whereas none were killed by 1.0% sodium polyanetholesulfonate when lysed blood was present . The possible clinical relevance of these results was reflected in the improved detection of meningococcemia in children when the Isolator 1.5 Microbial tube was compared with a conventional broth system.

Lancet, 1984 Jun 16, 1(8390), 1339 - 42
Meningococcal disease and season in sub-Saharan Africa; Greenwood BM et al.; The incidence of meningococcal disease varies seasonally in both tropical and temperate countries . This association is most apparent in sub- Saharan Africa, where almost all epidemics start in the dry season and abate during the rains . Meningococcal carriage rates do not vary with season either in Africa or in temperate countries, suggesting that seasonal factors have little influence on the frequency of meningococcal transmission . It is suggested that changes in the ratio of clinical to subclinical cases of infection are more important than changes in the frequency of transmission in producing seasonal variations in the incidence of meningococcal disease . Some evidence to support this hypothesis was obtained during an epidemic of group A meningococcal disease in northern Nigeria in 1977-79.

J Neurosurg Nurs, 1984 Jun, 16(3), 134 - 9
Meningococcemia: a case report; Galanes S; Meningococci in their pathogenic state can result in meningitis and/or meningococcemia . Fulminant meningococcemia has a high fatality rate and encompasses multiple complications which occur concurrently . Only with immediate and intensive care treatment can there be any hope of survival . Even with survival of the disease, the resulting complications and treatments can be overwhelming . The case report clearly demonstrates the extensiveness of the disease, but also displays a positive outcome in this particular case.

NIPH Ann, 1984 Jun, 7(1), 3 - 11
Late sequelae after meningococcal disease . A controlled study in young men; Sander J et al.; The occurrence of sequelae 3-15 years after meningococcal disease has been investigated in a study on 71 patients and 64 controls . The patients were young men, aged 18 to 24 years at the time the disease was contracted . Participants filled in a questionnaire on possible symptoms . Audiometry and EEG were also carried out . The response rates were 84% among patients and 75% among controls . We found that 61% of the patients had one or more symptoms of possible sequelae compared to 20% in the control group (p less than 0.001) . The symptoms were generally light and of mental or neurological type . Among the patients 13% stated that they had obvious complaints commonly attributed to meningococcal disease, compared to 2% only in the controls (p less than 0.05) . Twenty-nine per cent of the patients stated that the disease had affected their education or working capacity . No statistical differences between patients and controls were demonstrated by audiological or EEG examinations . In only one single ear could deafness unequivocally be attributed to the disease.

Ann Trop Med Parasitol, 1984 Jun, 78(3), 265 - 71
Malumfashi Endemic Diseases Research Project, XXI . Pointers to causes of death in the Malumfashi area, northern Nigeria; Bradley AK et al.; For 228 of 425 deaths (54%) occurring among 26 100 people of known age in the Malumfashi area of northern Nigeria, data were collected on symptoms present prior to death . Information was obtained on monthly registration visits, as part of demographic investigations, and data for the period November 1977-October 1978 have been analysed . Enumerators used a carefully prepared list of 25 symptoms to elicit information from relatives of the deceased . Pyrexia, diarrhoea and measles accounted for 77% of all deaths . Epidemiological determinants were responsible for all cases of meningococcal infections in the dry season and most cases of diarrhoea in the wet season . Most deaths attributed to measles occurred in the late dry season and early wet season . Epidemics of measles seemed to be localized at any one time in certain villages and the micro-epidemiology of this feature is considered . Malaria does not appear to be responsible for all deaths from pyrexia in the nought to four age group.

Acta Pathol Microbiol Immunol Scand {B}, 1984 Jun, 92(3), 159 - 63
Inhibitory spectrum of bacteriocin-like agents from Neisseria meningitidis; Jyssum K et al.; Bacteriocin-like agents from five strains of Neisseria meningitidis were active against other meningococci and some other Neisseria species . Meningococci belonging to the same serogroup or serotype could be subdivided into distinct bacteriocin types . Insensitivity to the inhibitory agents was observed more frequently among serologically groupable strains than among non-groupable . Strains belonging to serogroup B were more often insensitive to the inhibitors released by four of the donor strains (P201, P213, P241, 99/79) than other groupable strains . Insensitivity to the bacteriocin-like activity of the fifth donor strain (77/79A) seemed to be evenly distributed among strains of different groups . Strains of serotype 15 were more often insensitive to the five inhibitors than strains belonging to other types . Group B and type 15 are most frequently observed among strains isolated from clinical cases in Norway.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Jun, (6), 31 - 5
{Natural reproduction of all stages of a generalized meningococcal infection in mice}; Mironova TK et al.; The present work is based on the direct relationship, revealed in our investigations, between the hyaluronidase activity of meningococcal strains and their capacity to penetrate into the blood and the liquor . The use of the intranasal route (i.e . the natural route) for infecting previously untreated mice with meningococci in the presence of hyaluronidase made it possible to follow the generalized form of meningococcal infection in all its stages from the period of incubation and microbial invasion to bacteriemia, accompanied by the penetration of the infective agent into the meninges, and toxinemia . This route of infection ensured the penetration of the infective agent, but the natural specific resistance of mice to meningococci prevented their multiplication with the subsequent liberation of a sufficient amount of endotoxin killing the animals . To overcome natural immunity and increase toxicity, actinomycin D was injected intraperitoneally in a volume of 0.5 ml (5 gamma) simultaneously with the administration of the microbial culture and hyaluronidase, thus ensuring 40-60% mortality among the animals . Our model of the generalized form of meningococcal infection can be used in the study of pathogenesis and for the development of the methods of treatment and microbiological diagnosis.

Pathol Biol (Paris), 1984 Jun, 32(5 Pt 2), 532 - 5
{Antibiotic sensitivity of meningococci isolated from patients and carriers}; Dabernat H et al.; Ninety-two strains of Neisseria meningitidis (twenty-four recovered from CSF, four from blood, and sixty-four from oropharyngeal swabs) were tested for susceptibility to penicillin, ampicillin, minocycline, chloramphenicol, rifampicin, erythromycin, spiramycin, josamycin, sulphamethoxazole, and trimethoprim . Antibiotic activity (MIC) was determined by agar dilution . Among the 92 cultures, strains were in the following decreasing order: group B, undefined groups, and group C . 75% of strains recovered from carriers and 50% of those recovered from CSF were susceptible to 8 mg/l of sulphamethoxazole . No strain was susceptible to trimethoprim (MIC 8 mg/l) . All strains were susceptible to penicillin (range MICs: 0.007-0.25; mean MIC: 0.06), ampicillin (0.015-0.5; 0.12), minocycline (0.03-0.05; 0.25), chloramphenicol (0.12-4; 0.5) . and rifampin (0.007-0.25; 0.015) . In vitro activity of macrolides was influenced by culture conditions . With 5 to 10% CO2, MICs were 2 to 4 times greater than those culture conditions . With 5 to 10% CO2, MICs were 2 to 4 times greater than those observed without CO2 . Josamycin was more active than erythromycin and spiramycin.

Ann Emerg Med, 1984 Jun, 13(6), 471 - 3
Gastrointestinal disease associated with meningococcemia; Werne CS; Despite the multiple organ involvement seen in meningococcal disease, there is little in the literature to support gastrointestinal symptoms as the predominant finding . In the past year four patients with meningococcemia and meningitis presented with gastrointestinal symptoms . In three cases the gastrointestinal findings were of such severity that the diagnosis of meningococcemia was obscured.

NIPH Ann, 1984 Jun, 7(1), 21 - 8
Restriction endonuclease fingerprinting of meningococcal DNA; Kristiansen BE et al.; We have successfully developed a restriction endonuclease fingerprinting (REF) technique for the study of meningococcal chromosomal DNA . A review of our application of this method in studies of meningococcal epidemiology and pathogenicity is given . By REF we could show that fingerprints of apparently identical B15 carrier strains were remarkably heterogeneous, whereas invasive B15 isolates possessed very similar fingerprints . We could also demonstrate REF heterogeneity among B15 isolates collected from cases with meningococcal disease and their close contacts during an outbreak of meningococcal disease in a military camp in North Norway . The REF technique has also proved valuable for our studies on meningococcal piliation and adherence . At present, we are studying 67 different meningococcal isolates collected from all parts of Norway during the MenOPP project.

J Clin Microbiol, 1984 Jun, 19(6), 763 - 5
Applications of restriction endonuclease fingerprinting of chromosomal DNA of Neisseria meningitidis; Bjorvatn B et al.; Restriction endonucleases are bacterial enzymes that cleave DNA at specific sites . The resulting DNA fragments may be separated electrophoretically in gel to form specific restriction patterns . In the present study, the restriction endonuclease method was successfully adapted to the analysis of the chromosomal DNA of Neisseria meningitidis . The endonucleases HindIII and EcoRI provided optimal restriction patterns of ca . 50 well-separated lines . The pattern of each bacterial isolate was characteristic, stable, and reproducible . Despite some general similarity, the restriction patterns of the closely related B15 meningococci were surprisingly heterogeneous.

Am J Med, 1984 May 15, 76(5A), 180 - 6
Treatment of skin and skin structure infections in the patient at risk; Sheagren JN; Infections of the skin and skin structures in patients at risk can be either primary or secondary . In the normal host, the most important primary dermal pathogens are the group A beta-hemolytic Streptococcus and Staphylococcus aureus . These organisms can spread rapidly and seed to distant sites . Secondary skin involvement occurs in several life-threatening bacteremic conditions in previously normal hosts, especially in those involving meningococci and S . aureus . In the compromised host, although the acute pyogenic bacteria just mentioned can be even more devastating, low grade pathogens or nonpathogenic members of the normal flora, or both, are commonly involved . Such organisms include gram-negative aerobic bacilli, a variety of anaerobes, several fungi, and the herpesviruses . Therapy of primary skin and skin structure infections invariably should include debridement along with antibiotic coverage . Debridement must be complete, opening all deep extensions of the primary infection and removing, to the extent possible, all foreign materials . In the normal host, antibiotic coverage must include a beta-lactamase-resistant antibiotic or vancomycin if beta-lactamase-resistant, antibiotic-resistant S . aureus could be involved . In the compromised host, signs of local inflammation may be reduced; yet, debridement must still be aggressive and antibiotic coverage broad . Neutropenic patients should be covered for Pseudomonas aeruginosa, requiring a combination of an antipseudomonal agent plus an aminoglycoside . Antifungal or antiviral therapy, or both, should be added in the severely compromised host in the proper setting, especially in patients not promptly responding to antibacterial measures . Attempts to enhance host defenses should be considered.

Pathol Biol (Paris), 1984 May, 32(5), 375 - 7
{Use of josamycin in the eradication of meningococcus}; Pautard JC et al.; Because of their in vitro and in vivo activity on Neisseria meningitidis, good salivary and tonsillar tissue levels, high safety and non-penetration through the meningeal barrier, macrolides are agents of choice for treating Meningococcus carriers . To assess the value of josamycin for eliminating Meningococci in carriers, we carried out a 14-month study with bacteriological control . 27 carriers identified (throat specimens) among contacts of 28 children with meningococcal meningitis hospitalized in Pediatrics at the Amiens and Toulouse CHU (teaching hospitals) were treated . Josamycin was given in a dosage of 50 mg/kg/day in children and 2 g/day in adults, in two divided doses daily, for six days . Bacteriologic control at the end of treatment showed that every study patient was free of Meningococci . In vitro, strains recovered from carriers were inhibited by josamycin at concentrations of 0.25 to 1 microgram/l . Given its safety and efficacy, josamycin is well suited to prophylaxis of meningococcal infections.

J Infect, 1984 May, 8(3), 264 - 73
Mortality in meningococcal disease in Belgium; De Wals P et al.; A survey of children admitted with meningococcal disease to 53 paediatric units in Belgium between 1975 and 1979 was made in order to assess the case mortality rate (CMR) and to identify risk factors associated with death . A total of 309 cases (226 bacteriologically confirmed and 83 unconfirmed) was recorded . The overall CMR was 6.1 per cent . It was 4.4 for bacteriologically confirmed cases and 10.8 for unconfirmed cases . The CMR was higher for septicaemia without meningitis (22.2 per cent) than for meningitis with or without signs of septicaemia (3.4 per cent) . The risk of death was not related to the sex or nationality of the patients . Age was a major determinant of the CMR, independently of the clinical picture . The highest risk of death was in children under one year of age . Poor socio-economic conditions were a significant risk factor . Failure to recognise the severity of the disease by some poorly educated mothers, and the admission of the patient to a hospital lacking adequate facilities for managing severely affected children, were the two significant causes of delay of adequate treatment.

Clin Orthop, 1984 May, (185), 214 - 9
Amputation following meningococcemia . A sequela to purpura fulminans; Jacobsen ST et al.; In five patients with purpura fulminans following meningitis, gangrene of the extremities developed . Four patients required amputations of the lower extremities and two patients of the upper extremities . The gangrene is caused by disseminated intravascular coagulation . In two patients epiphyseal damage and subsequent angular deformities developed . The orthopedic surgeon should be consulted early because aponeurectomy may save an extremity . Some method of temporary skin coverage should be considered at the time of initial debridement and aponeurectomy . Early skin grafts are frequently rejected because the extent of necrosis has not declared itself, necessitating further grafting, which results in multiple painful and unsightly donor scars . Stump problems due to less than satisfactory skin coverage, stump overgrowth, joint contractures, and epiphyseal damage are later complications.

Helv Paediatr Acta, 1984 May, 39(2), 187 - 92
Pneumonia associated with meningococcal bacteremia and/or meningitis; Llorens-Terol J et al.; Four children between 5 and 12 years of age had pneumonia as a secondary complication of meningococcal bacteremia and/or meningitis . The diagnosis of meningococcal disease was established by culture of blood and/or cerebrospinal fluid . Fine inspiratory rales were found in one patient . In the other three cases pulmonary infiltrates were evidenced on chest roentgenogram . All patients recovered with penicillin G sodium therapy.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 May, 257(1), 195 - 203
Meningococcal meningitis in CSR: a preepidemic situation?
Kuzemenska P, Kriz B, Svandova E.
Meningococcal meningitis has become a problem in many European countries, with epidemics occurring during the past 10-15 years . There have also been outbreaks in some non-European countries . The latest meningococcal meningitis epidemic recorded in the CSR (Czech Socialist Republic) occurred in 1953, with the morbidity reaching 14.8 per 100 000 population . After the mid 1950's there was a gradual decline in morbidity, the lowest value (0.3 per 100 000 population) being reached in 1974 . Since 1975 there has been a continual rise in morbidity, the value notified for 1982 was 1.2 per 100 000 population . An analysis of the epidemiological situation in meningococcal meningitis in CSR for the past 30 years was performed . Different indicators of the onset of epidemics were evaluated . Shift in the age distribution of patients was found to be the most valuable sign of changing epidemiological situtation . An attempt was made to prognosticate mathematically its further development . The analysis of the epidemiological data suggests that CSR is in a preepidemic situation . This finding is all the more important because a change has been found in the serogroup and serotype patterns of Neisseria meningitidis strains isolated from cerebrospinal fluid.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 May, 257(1), 185 - 94
Neisseria meningitidis strains isolated in CSR from cerebrospinal fluid: preepidemic shift in serogroup and serotype distribution?
Kuzemenska P.
Antigenic properties of N . meningitidis strains isolated from CSF in CSR were surveyed . Capsular antigens (serogroups) were tested from 1970, noncapsular antigens (serotypes) from 1975 . Results up to the end of 1982 are presented . In 1980 shifts were encountered in the distribution of both capsular and noncapsular antigens . Serogroups . Group B predominated throughout the surveillance period, but from 1980 this predominance was significantly lower . Group C was the second most frequent throughout the observed period, but its frequency rose significantly from 1980 and stayed high . Group A was the third in frequency all the time, its relative prevalence increased (but not significantly) from 1980 . Serotypes . Serotype 2 predominated during the whole period, but its predominance rose significantly from 1980 . Serotype 4 was second in frequency, but from 1980 its frequency also increased significantly . Serotypes other than 2 or 4 decreased significantly in frequency and variability from 1980, also nontypable strains decreased significantly from 1980 . Changes in the distribution of the capsular and noncapsular antigens on N . meningitidis strains from CSR are characteristic of epidemic situation . The present finding is all the more serious because it comes in a context of rising meningococcal morbidity and a shift in the morbidity into older age groups.

Infect Immun, 1984 May, 44(2), 320 - 5
Mechanism of impaired iron release by the reticuloendothelial system during the hypoferremic phase of experimental Neisseria meningitidis infection in mice; Letendre ED et al.; Hypoferremia, the reduction of plasma transferrin iron levels during infection, has been shown to control Neisseria meningitidis infection in mice . The exact nature of the mechanism that regulates this response has been obscure . We have previously shown that hypoferremia does not result from an accelerated removal of iron from the plasma transferrin pool . In this study, we have examined the processing of iron by the reticuloendothelial system during infection . Normal and hypoferremic meningococcus-infected mice were injected with 59Fe-labeled erythrocytes . Kinetics of uptake and redistribution of the label indicated that during the hypoferremic phase of the infection, reticuloendothelial system-processed iron was not returned to the plasma transferrin pool . Fractionation of hepatic cellular compartments showed that this impaired release of iron resulted from a preferential incorporation of heme-derived iron into the intracellular ferritin pool during the hypoferremic phase of the infection . These findings indicate that this withholding of iron within the intracellular pool leads to hypoferremia and therefore denies the extracellular pathogen its essential iron.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Apr, (4), 32 - 7
{Ultrastructure of the meningococcus in logarithmic and stationary development phases}; Vysotskii VV et al.; The complex study of Neisseria meningitidis cultures A-208 in the time course of their development has disclosed that broth cultures in the logarithmic and stationary phases of their development are most valid on account of all their biological properties (the specific character of the reaction of agglutination, viability, the morphology of colonies and cells in light and electron microscopy) . The use of scanning electron microscopy has made it possible to reveal bubbly endotoxin excretion in N . meningitidis and funnel-shaped depressions on their surface corresponding, probably, to nucleoid epicenters . In ultrathin sections some previously unknown features of the ultrastructure of N . meningitidis in the logarithmic and stationary phase of their development have been detected: (a) the morphological heterogeneity of N . meningitidis represented by cells of the "light" (L) and "dark" (D) types; (b) the surface structures of meningococcal cells from the cultures in the stationary phase of development show the tendency to smoothing out, which is accompanied by their sharper differentiation.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Apr, (4), 108 - 11
{Effect of Neisseria meningitidis on the humoral response of various strains of mice immunized with ram erythrocytes}; Petrov AB et al.; The capacity of heat-killed meningococci and the polysaccharide-protein-lipopolysaccharide fraction ( PPLF ) isolated from the microbial cell wall for changing nonspecific immunological reactivity was studied . In this investigation CBA mice with high response and C57BL/6 mice with low response to sheep red blood cells (SRBC) were used . Heat-killed N . meningitidis, serogroup A, and PPLF , serogroups A and B, were found to enhance and suppress humoral response to the heterologous antigen . The effect of modulation depended on the dose of the antigen, the serogroup of meningococci, the scheme of the experiment and the strain of mice . The immune response of the vaccinated animals to the heterologous antigen was characterized by the following stages: the state of the adjuvant effect was replaced by the state of temporary immunodeficiency and then by enhanced response to SRBC.

Acta Pathol Microbiol Immunol Scand {B}, 1984 Apr, 92(2), 73 - 7
Effect of temperature on the survival of Neisseria meningitidis; Hoiby EA et al.; The effect of different temperatures and variations in temperature on the survival of Neisseria meningitidis in modified Stuart transport medium and in human cerebrospinal fluid (CSF) has been investigated . The meningococcal strains examined died quickly during storage at 37 degrees C, while storage at 4 degrees C and 22 degrees C caused only a moderate decrease in their viability . Short periods of temperature variations during storage at 22 degrees C in transport medium were found to be harmful only when the specimens were kept at -20 degrees C for these short periods . According to our results, 37 degrees C storage temperature cannot be recommended for specimens such as those examined . As 4 degrees C may be harmful to H . influenzae one cannot generally recommend keeping specimens from meningitis patients in refrigerator until analyzed . Room temperature therefore seems preferable . Specimens inoculated onto growth-supporting media should of course contrarily be incubated at 35-37 degrees C.

Trop Doct, 1984 Apr, 14(2), 61 - 6
Treatment and prevention of meningococcal disease; Greenwood BM; Meningococcal meningitis responds well to treatment and, even when this is given in unsatisfactory surroundings, recovery rates of 90-95% can be expected . A few patients are left with permanent disabilities, such as deafness, but most make a complete recovery . Mild cases of acute meningococcaemia are sometimes encountered . In Africa such patients are seen most frequently at the end of an epidemic, but in general the outlook for patients with this condition is poor . Patients who have hypotension or impairment of consciousness often die, even when they receive optimum treatment . Meningococcal disease can be prevented by chemoprophylaxis, vaccination or a combination of both . Great care is needed in deciding upon the control strategy which should be adopted in any particular set of circumstances . Studies on the cost effectiveness of different approaches to the prevention of meningococcal disease in developing countries are needed urgently.

J Clin Pathol, 1984 Apr, 37(4), 428 - 32
Inhibitory effect of cerebrospinal fluid on the growth of meningococci and pneumococci; Hassan-King M et al.; Initial cerebrospinal fluid (CSF) samples obtained from patients with pneumococcal meningitis usually contain far greater numbers of bacteria than initial CSF samples obtained from patients with meningococcal meningitis . Normal CSF was found to have an inhibitory effect on the growth of group A meningococci but not on type 1 pneumococci . The inhibitory effect of normal CSF was abolished by dialysis, indicating that the inhibitory factor has a low molecular weight . Heating normal CSF to 62.5 degrees C for 30 min resulted in a considerable reduction in the inhibitory effect, indicating that the inhibitory factor is heat labile.

Vopr Med Khim, 1984 Mar-Apr, 30(2), 28 - 33
{Lipid composition of erythrocyte membranes and blood serum in meningococcal infections in children}; Simovan'ian EM et al.; Significant impairments of lipid homeostasis were observed in lipid composition of erythrocyte membranes and blood serum in acute period of meningococcal infection, involving pronounced alterations in content of phospholipids, phospholipid fractions, total cholesterol, unesterified fatty acids as well as activation of phospholipase A2 . The degree and pattern of dyslipidemia depended on clinical form, severity of the disease and age of children . The most serious deteriorations were found in the patients with a mixed form of the disease, at early age and during the critical period of meningitis . Studies of lipid composition in erythrocyte membranes, as compared with that of blood serum, enabled to obtain more clear-cut and certain information on the state of lipid homeostasis in the disease . Estimation of main components of lipid metabolism might be used as informative criterion for evaluation of the disease severity and for prognosis of unfavourable outcome.

J Clin Microbiol, 1984 Mar, 19(3), 383 - 7
Diagnostic value of interactions between members of the family Neisseriaceae and lectins; Doyle RJ et al.; The lectin slide agglutination test for Neisseria gonorrhoeae has been modified and improved . Results show that wheat germ agglutinin and soybean lectin agglutinate 100% (193 of 193 tested) of clinical isolates of N . gonorrhoeae . Lectin-reactive meningococci can be readily identified by the hydrolysis of gamma-glutamyl-beta-naphthylamide . Branhamella catarrhalis, Neisseria lactamica, Neisseria sicca, Neisseria subflava, Neisseria perflava, and meningococcal serogroups A, B, C, X, Y, and Z do not interfere with the positive identification of N . gonorrhoeae . The frequently encountered problem of autoagglutination of members of the family Neisseriaceae may be circumvented by a short treatment of cellular suspensions with DNase . Based on agglutination assays, the enzyme treatment did not result in a loss of wheat germ agglutinin receptors from the bacteria . The lectin agglutination test, coupled with the gamma-glutamyl aminopeptidase assay, is proposed as a rapid and accurate means of identifying clinical isolates of gonococci.

Zh Mikrobiol Epidemiol Immunobiol, 1984 Mar, (3), 106 - 12
{Immunological effectiveness of a dried group-A meningococcal polysaccharide vaccine}; Alliluev AP et al.; The immunological effectiveness of dried group A meningococcal polysaccharide vaccine, developed at the Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow, for children aged 5-14 years was studied . The intensiveness of the immune response of children to 0.5 ml of the vaccine introduced in a single injection was evaluated by a rise in the level of agglutinating antibodies to group A meningococcal polysaccharide in the sera of the vaccinees 3-4 weeks after immunization with the following optimum doses: 25 micrograms for children aged 5-8 years, 50 micrograms for children aged 9-13 years and 75 micrograms for children aged 14 years and over . The vaccine was shown to be highly immunogenic . Antibodies to group A meningococcal polysaccharide were identified as IgM . These antibodies in a titer of 1:40 and higher could be detected in 90% of the vaccinated children in the younger age group, 7 months after immunization.

J Infect Dis, 1984 Mar, 149(3), 387 - 96
Class-specific human bactericidal antibodies to capsular and noncapsular surface antigens of Neisseria meningitidis; Skevakis L et al.; Bactericidal and enzyme-linked immunosorbent assays were used to determine the immunoglobulin classes responsible for group- and type-specific immunity to Neisseria meningitidis among healthy, unvaccinated individuals and persons who received group-B N meningitidis polysaccharide-serotype-2 protein vaccine . Bactericidal antibodies to the group B polysaccharide were primarily IgM; only a few individuals had both IgM and IgG antibodies . IgG bactericidal antibodies were detected only in those individuals with high IgM-antibody levels to group B meningococci . Increased levels of bactericidal antibodies to the group-B polysaccharide were infrequently found in vaccinees, possibly because of high prevaccination bactericidal-antibody levels . Bactericidal antibodies to the group-C polysaccharide were IgM, IgG, or both . Vaccine-induced antibodies to lipopolysaccharide were not bactericidal for a group-C serotype-2 strain with the lipopolysaccharide immunotype of the vaccine strain.

Am J Public Health, 1984 Mar, 74(3), 253 - 4
Group A meningococcal disease in skid rows: epidemiology and implications for control; Filice GA et al.; Interviews conducted during outbreaks of group A meningococcal disease in skid row communities suggested that heavy alcohol use was associated with increased risk of disease . Frequent moving within skid row and from one skid row to another was characteristic of a subpopulation with increased risk of disease and may have facilitated spread within and between skid rows . The observations discussed herein have important implications for control of communicable diseases in and near skid rows.

J Immunol Methods, 1984 Feb 24, 67(1), 1 - 11
Use of a zwitterionic detergent for the restoration of the antibody-binding capacity of electroblotted meningococcal outer membrane proteins; Mandrell RE et al.; A method is described for the partial restoration of the antibody-binding capacity of meningococcal class 2 outer membrane proteins (40-42 K molecular weight) following denaturation (dissociation) in boiling sodium dodecyl sulfate (SDS) . The method relies on the presence of 0.1-0.4% zwitterionic detergent in the electrode buffer during the electroblot transfer of proteins from SDS-polyacrylamide gels to nitrocellulose paper . Meningococcal class 2 proteins which had lost their earlier capacity to bind mouse monoclonal antibodies in the normal blot procedure after SDS-polyacrylamide gel electrophoresis, bound monoclonal antibodies following the addition of the zwitterionic detergent to the blot buffer . Human post-vaccination anti-class 2 protein antibodies reacted with serotype 2a class 2 protein in a similar manner . This simple modification to the electroblot procedure proved helpful in identifying mouse monoclonal antibodies and human antibodies specific for native meningococcal class 2 proteins.

An Esp Pediatr, 1984 Feb 15, 20(2), 85 - 90
{Naloxone and endotoxic shock: a wonder drug?}; Valdivielso A et al.; Naloxone clorhidrate was administered intravenously to 15 patients with endotoxic shock and refractary hypotension, following meningococcal sepsis . Doses used were between 0.01-0.2 mg/kg . Three patients (two of them with moderate shock) showed an increase in sistolic arterial pressure, which was maintained and above 20 mm/Hg . Among the rest of them (except one with severe shock) naloxone action was non-existent in nine cases, or with short action and without answer to next doses in other three . Eleven patients died . A blood pressure increase was maintained only in two of the four survivors . Usefulness of naloxone in this kind of patients is not clear . Presence in endotoxin shock of a variety of refractory factors besides beta endorphins, greatly limits therapeutic efficiency of this drug.

Br Med J (Clin Res Ed), 1984 Feb 11, 288(6415), 439 - 41
Meningococcal septicaemia treated with combined plasmapheresis and leucapheresis or with blood exchange; Bjorvatn B et al.; Mortality among patients suffering from meningococcal septicaemia has reached nearly 50% in parts of northern Norway despite intensive care . The activation of complement and blood cells by endotoxin is assumed to be the cause of most of the associated pathophysiological changes . Consequently, it would seem logical to remove such constituents either by combined plasmapheresis and leucapheresis or by blood exchange in patients with a fatal prognosis . Three patients were treated with plasmapheresis and leucapheresis and one with blood exchange . All recovered without sequelae, and no complications or serious problems caused by these procedures were observed . It is concluded that either combined leucapheresis and plasmapheresis or blood exchange is well tolerated and a valuable supplement to conventional intensive care in fulminant meningococcal septicaemia.

Clin Chim Acta, 1984 Jan 31, 136(2-3), 173 - 8
The latency of serum acute phase proteins in meningococcal septicemia, with special emphasis on lactoferrin; Gutteberg TJ et al.; Serum lactoferrin concentrations were elevated in almost all children with meningococcal septicemia, in whom the disease had been clinically apparent for less than 18 hours, while the concentrations were normal or only moderately elevated in patients who had had the disease longer before being admitted . Concentrations of C-reactive protein (CRP) were markedly elevated, even with a time lapse of less than six hours, making this the most suitable parameter for the early diagnosis of severe meningococcal infection . Following an operative injury on children the lactoferrin concentrations changed very little . More than six hours after an operation, however, a marked increase in CRP-values was observed, possibly indicating differentiation of this response from that of bacterial infection . The concomitant study of serum alpha 1-antitrypsin, alpha 1-antichymotrypsin, orosomucoid and haptoglobin did not uncover results of great significance with regard to early changes.

Schweiz Med Wochenschr, 1984 Jan 28, 114(4), 136 - 40
{Lethality and danger of 14 types of purulent meningitis in the pre-ampicillin and in the ampicillin period . Synoptic overview of an epidemiologic study}; Buchs S et al.; Based on epidemiological data in the western literature, the lethality of purulent meningitis over the last 32 years has been assessed . 14 types of meningitis (11 with frequent, 3 with rare etiologic agents) were investigated, and the results of the pre-ampicillin period (1948-1962) compared with the post-ampicillin period (1963-1979) . Results: during the ampicillin period lethality decreased significantly in patients aged below 60 years . For meningitis caused by salmonellae and certain strains of streptococci, the decrease was not statistically significant . In the population over 60, however, no significant decrease occurred, and the lethality of meningococcal meningitis even increased significantly . Presentation in graph form shows these findings very clearly, and comparison with the lethality of Hemophilus influenzae meningitis serves to express the potential danger of all these meningitis types numerically.

J Infect, 1984 Jan, 8(1), 49 - 55
Outbreak of infection caused by Neisseria meningitidis group C type 2 in a nursery; Saez-Nieto JA et al.; An outbreak of meningococcal infection which took place in a nursery in Rioja, Spain, is reported . Between November 1981 and February 1982, 11 patients had meningitis with or without septicaemia . Two died . Three meningococcal strains from the patients isolated were studied . All three were group C type 2 and were resistant to sulphadiazine (MIC 50 mg/l) but susceptible to penicillin, ampicillin, chloramphenicol, rifampicin and spiramycin . This outbreak took place during an epidemic in which serogroup B was the most prevalent in Spain . Two surveys before and after chemoprophylaxis were made to determine the carrier rate in the nursery population . The strain causing the outbreak was found in 2.5 and 4 per cent of persons respectively . Rifampicin was administered to all carriers after the first survey and to carriers of the virulent strain after the second survey . The remaining children were given polysaccharide C vaccine . No more cases arose after this last prophylactic measure.

Biomed Pharmacother, 1984, 38(5), 277 - 9
{Circulating calcitonin in fulminating purpura in children}; Mallet E et al.; Hypocalcaemia may complicate the treatment of fulminating meningococcaemia in children . In an attempt to elucidate the pathophysiology of the hypocalcaemia, we have measured accompanying changes in blood levels of calcitonin (BW-336-6 antiserum) and parathyroid hormone (C-terminal antiserum IRE) . Ten children aged 1-11 years with fulminating meningococcaemia are studied . The high PTH levels may be a response to the hypocalcaemia, but the hypercalcitoninaemia seems inappropriate . Provided the immunoreactivity of the calcitonin detected corresponds to calcitonin 1-32, the origin of this hypercalcitoninaemia remains to be explained.

Intensive Care Med, 1984, 10(5), 245 - 9
An extreme form of the hyperdynamic syndrome in septic shock; Baumgartner JD et al.; We classified 41 patients in septic shock on the basis of cardiac index (CI) after volume expansion with plasma protein solution, in order to obtain adequate filling pressures . Five had decreased CI (less than 3.5 1/min per m2), 31 had moderately increased CI (3.5 - 7.0 1/min per m2) and 5 had extreme hyperdynamic shock with CI superior to 7.0 1/min per m2 . Among the patients with increased CI, those with extreme hyperdynamic state (EHS) had lower total systemic and pulmonary arteriolar resistances (370 vs 658 and 52 vs 119 dynes X s X cm-5, respectively) and a higher stroke index (67 vs 46 ml/m2), in spite of similar right atrial pressures . In this latter group, blood lactate was higher (6.5 vs 2.1 mmol/l), acidosis was more severe and coagulation disorders more pronounced; all five patients maintained an extremely high CI until death, which supervened after a brief episode of sinus bradycardia . A similar clinical course was rarely observed in the remaining moderately hyperdynamic group, in which mortality rate was significantly lower (35%) . Three of five patients with EHS (compared to 2 of 31 in the moderately hyperdynamic group) had liver cirrhosis, the fourth died of fulminant meningococcemia and the fifth had prolonged polymicrobial bacteremia before adequate treatment was begun . Thus, underlying liver disease or particularly severe and uncontrolled infection seems to predispose to EHS . It is concluded that septic shock with extremely high cardiac output and excessively low peripheral resistances represents a distinct subset with more severe metabolic and coagulation disorders, an unusual hemodynamic evolution and a particularly poor prognosis.

Trans R Soc Trop Med Hyg, 1984, 78(3), 399 - 403
A field trial of a single intramuscular injection of long-acting chloramphenicol in the treatment of meningococcal meningitis; Puddicombe JB et al.; During an epidemic of meningococcal meningitis 86 patients with symptoms and signs of meningitis were treated with a single intramuscular injection of a long-acting oily preparation of chloramphenicol (Tifomycine) . Treatment was given by auxiliary medical staff who worked in four separate village dispensaries under the supervision of the local medical officer . The clinical response to treatment was satisfactory; 79 of 86 patients (92%) recovered fully with few residual disabilities . There were five deaths (5.8%) but a definite diagnosis of meningococcal meningitis was established in only one of these patients . Treatment was changed because of a poor clinical response in two further patients . Diagnosis was eventually proved in 45 patients (52%) . The response to treatment of patients in this group was similar to that observed in the remaining 41 patients . The results of this preliminary study show that a single dose injection of a long-acting chloramphenicol is of value in the management of epidemics of meningococcal meningitis in rural areas because patients can be treated locally and early in their village dispensaries, thereby minimizing the need to transport them to urban hospitals which are often distant and congested.

Infection, 1984, 12 Suppl 1, S35 - 43
Epidemiology of meningococcal meningitis in Sahel and Mongolia; Skalova R; The epidemiological situation of meningococcal meningitis in the African meningitis belt and in Mongolia are presented . Studies on bacterial air pollution have been conducted in different types of dwellings in the two regions affected by meningococcal meningitis . Results have shown that during the dry (meningitis) season the air in dwellings is much more contaminated by bacteria, including those of oral origin, as a consequence of environmental conditions (crowding, activity, ventilation) . A significant correlation between the bacterial counts and the incidence of meningococcal disease has been demonstrated . On the basis of the results obtained, measures can be recommended which could be used in the prevention of meningitis, especially in the case of a high prevalence of serogroups of meningococci other than those which can be efficiently controlled by immunization.

Scand J Infect Dis, 1984, 16(3), 257 - 66
Effect of benzylpenicillin in mice infected with endotoxin-liberating or non-liberating variant strains of Neisseria meningitidis; Andersen BM et al.; The effect of benzylpenicillin treatment was studied in mice infected intraperitoneally (i.p.) with endotoxin-liberating (E+) and non-liberating (E-) meningococci derived from the same original serogroup B strain . The E+ meningococci were significantly more virulent to mice than the E- variants in untreated animals (p less than 0.001) . Large doses of benzylpenicillin given intravenously (i.v.) immediately after i.p . inoculation of E+ or E- meningococci resulted in complete, or almost complete survival . When treatment started later the number of surviving E- infected animals increased in all treatment regimens . By contrast, E+ infected animals had one or more treatment groups in all regimens that did not respond to benzylpenicillin at all . Benzylpenicillin treatment was given over a period of time as intermittent, regular i.v . doses, or as a depot preparation subcutaneously (s.c.) . The mortality observed in E+ infected mice after benzylpenicillin i.v . was 75%, after benzylpenicillin procaine s.c . 82.5%, while animals receiving only saline i.v . had a mortality of 67.5% . The corresponding mortalities for E- infected animals were 15% (p = 0.0014), 42.5%, and 42.5%, respectively.

Scand J Infect Dis, 1984, 16(3), 247 - 54
Endotoxin liberation and invasivity of Neisseria meningitidis; Andersen BM et al.; The relationship between endotoxin liberation and invasiveness was studied in 50 strains of Neisseria meningitidis isolated from blood or cerebrospinal fluid (CSF) of 16 patients with invasive disease, from nasopharynx of 9 patients with upper respiratory tract symptoms, and from nasopharynx and rectum (1, serogroup W-135) in 25 persons examined for venereal disease . Meningococci varied in their ability to liberate endotoxin . Free endotoxin was partly a function of growth and seemed to be associated with certain properties of the individual strain . Strains isolated for patients with invasive disease liberated significantly more endotoxin than strains isolated from the venereal group (p less than 0.002) . All 16 invasive strains were sulfonamide resistant, against 5/9 strains from patients with upper respiratory disease symptoms and only 4/25 strains from the venereal group . The difference between the invasive group and the venereal group was significant (p less than 0.002) . Serogroup A, B, C meningococci liberated significantly more endotoxin than non-A, B, C strains (p = 0.01, and serogroup A, B, C strains isolated from nasopharynx tended to have a higher endotoxin release than non-A, B, C strains isolated from the same place (not significant) . Serogroup B meningococci were most frequently isolated both from patients with invasive disease and from the nasopharynx of the persons examined for venereal disease . Serogroup B meningococci had significantly more free endotoxin when isolated from blood or CSF than when isolated from nasopharynx of presumably healthy persons (p = 0.002).

J Biol Stand, 1984, 12(2), 159 - 66
Detection of blood group A-like substance in bacterial and viral vaccines by countercurrent immunoelectrophoresis using Helix pomatia lectin; Oravec LS et al.; The technique of countercurrent immunoelectrophoresis (CI), using the N-acetyl glucosamine-binding lectin from Helix pomatia, provided a rapid, sensitive, inexpensive, specific and reliable method for assaying blood group A-like substances in both bacterial and viral vaccines . Blood group A-like substance was detected in the pneumococcal polysaccharide vaccine manufactured by Merck Sharp & Dohme up to 1981 and in a staphylococcus vaccine ( Staphage Lysate) manufactured by Delmont Laboratories . Other US licensed vaccines, including diphtheria and tetanus toxoids, pertussis, meningococcal polysaccharide and influenza vaccines, did not contain detectable amounts of this substance . Human anti-A globulins did not provide a satisfactory reagent for the CI assay because they contained precipitating activities to the vaccine components.

Am J Med, 1984 Jan, 76(1), 115 - 21
Antibody responses to meningococcal polysaccharide vaccine in adults without a spleen; Ruben FL et al.; Asplenic persons are at risk for the development of overwhelming sepsis from certain encapsulated bacteria, including meningococci . Since it is not known if asplenic persons can have antibody responses, this study compared such responses following bivalent groups A and C meningococcal polysaccharide vaccine in 22 asplenic subjects and healthy control subjects . There were no adverse reactions to the vaccine . Antibody responses were measured using a solid-phase radioimmune assay; results were compiled for both seroconversions and changes in mean antibody titers of IgG, IgA, and IgM classes . Subjects who underwent splenectomy for trauma and control subjects with spleens showed a polyclonal antibody response to both vaccine antigens . Those persons who underwent splenectomy for nonlymphoid tumors had nearly as good a response as normal subjects . By contrast, asplenic subjects with lymphoid tumors who had received prior chemotherapy and radiotherapy had poor responses to both antigens . It is concluded that meningococcal vaccine is immunogenic in asplenic persons, with the aforementioned exceptions, and that this vaccine should be routinely administered to such persons.

Infect Immun, 1984 Jan, 43(1), 407 - 12
Conjugation of meningococcal lipopolysaccharide R-type oligosaccharides to tetanus toxoid as route to a potential vaccine against group B Neisseria meningitidis; Jennings HJ et al.; Oligosaccharides were obtained by the mild acid hydrolysis of the lipopolysaccharides from a number of different strains of Neisseria meningitidis, serotypes L2, L3, L4, L5, and L10 . The dephosphorylated oligosaccharides were conjugated to tetanus toxoid as their 2-(4-isothiocyanatophenyl)-ethylamine derivatives, which resulted in the incorporation of from 18 to 38 oligosaccharides per molecule of tetanus toxoid . When injected in rabbits, the conjugates produced oligosaccharide-specific antibodies which were predominantly serologically specific but which also exhibited some cross-reactivity . These serological results can be attributed to regions of structural dissimilarity and similarity within the oligosaccharides . The oligosaccharide-specific antibodies were also lipopolysaccharide serotype specific, thus indicating that the oligosaccharides are the determinants associated with this serotype specificity . Consistent with the serological results, the conjugate antisera were bactericidal for the homologous serotype meningococcal organisms and in some cases for heterologous serotype organisms.

Zh Nevropatol Psikhiatr Im S S Korsakova, 1984, 84(10), 1493 - 8
{Bioelectric activity of the brain in hypertoxic forms of meningococcal infection in children}; Shipitsyna LM et al.; Children with the generalized form of meningococcal infection aggravated by infectious-toxic shock and brain oedema showed a correlation between symptoms of central nervous system dysfunction and diffuse disturbances of cerebral bioelectrical activity combined with the attenuation of the intercentral relationships of the cortical zones which was most marked in the anterior portions of the left hemisphere . With progressive improvement of the patient, the links between the lobular and temporal zones, especially in the right hemisphere, became stronger which seems to indicate the strengthening of the cortical influence on the limbic diencephalic structures of the brain which activates the child's protective and adaptive reactions.

Schweiz Med Wochenschr, 1983 Dec 10, 113(49), 1857 - 8
{Neisseria meningitidis B and E . coli K1: different genes causing the production of an identical capsule . Preliminary communication}; Hirschel B et al.; E . coli of type K 1 and meningococcus of group B have identical capsules . Using gene cloning and nuclear hybridization, the authors show that the genes responsible for capsule production differ in the two bacteria (no DNA homology).

NIPH Ann, 1983 Dec, 6(2), 183 - 90, 202-3
The occurrence and features of hemorrhagic skin lesions in 115 cases of systemic meningococcal disease; Brandtzaeg P et al.; Hemorrhagic skin lesions (SH) are common in systemic meningococcal disease (MCd) and are very importance in differential diagnosis . The occurrence of SH in 115 MCd cases in relation to outcome (sequelae or death) and diagnostic category of MCd is described as well as the occurrence of SH in 61 control patients with similar referral diagnoses . We found SH in 77% of the MCd patients and about 20% of the control patients . The SH in the latter group tended to be small, localized and few . Multiple SH, a larger size and a generalized distribution was found in MCd patients with a graver prognosis . Health workers and particularly the public should learn more about SH in MCd and their significance . This may improve the care of MCd patients in promoting earlier diagnosis and therapy.

NIPH Ann, 1983 Dec, 6(2), 175 - 81
The early phase of meningococcal disease; Tonjum T et al.; In a prospective case control study in Norway during the winter 1981-1982, 115 patients with systemic meningococcal disease were compared with 61 patient controls . Initially, skin bleedings, reduced general condition and consciousness, and body pain were seen more often, but irritability less often in meningococcal patients than in the patient controls . The meningococcal patients presented symptoms typical of infectious diseases in general . Symptoms that correlated with a poor prognosis of the meningococcal disease were reduced consciousness, cyanosis, and early diarrhea . The mean time interval from start of the meningococcal disease until admission to hospital was 34 hours . No deaths occurred when less than six hours elapsed before it was decided to admit the patient . All fatal cases were admitted by the first doctor who saw the meningococcal patient . Contact with the family doctor does not seem to have reduced the risk of death . To avoid unnecessary delays, access to hospitals should be facilitated, and efforts should be made to shorten the time interval before patients with relevant symptoms are seen by a doctor.

NIPH Ann, 1983 Dec, 6(2), 169 - 73
Factors preceding the onset of meningococcal disease, with special emphasis on passive smoking, symptoms of ill health; Haneberg B et al.; In a prospective study of 115 patients with systemic meningococcal disease, 61 control patients and 293 population controls, environmental and other factors which preceded the illness and which might have influenced the acquisition and case fatality rate of the meningococcal disease were investigated . Passive smoking in children under 12 year of age, stressful events, and symptoms and signs of preceding illness within the last two weeks were significantly more frequent in meningococcal patients than among the population controls . In contrast, those patients who had been exposed to stressful events, or who had symptoms or signs of ill-health preceding the meningococcal disease, had significantly reduced case fatality rates as compared to those who had not had any such experiences . Passive smoking remains a factor of great interest for further studies and intervention.

NIPH Ann, 1983 Dec, 6(2), 155 - 68
An epidemiological, clinical and microbiological follow-up study of incident meningococcal disease cases in Norway, winter 1981-1982 . Material and epidemiology in the MenOPP project; Gedde-Dahl TW et al.; To investigate the relative importance of the many possible influencing factors and developmental traits of systemic meningococcal disease (MCd) in the practical Norwegian context, a comprehensive multipurpose case control study was carried out during the winter of 1981-1982 on incident cases in the whole country . The design of the study, the MenOPP project, is outlined . The main inclusion criteria for patients were suspected bacterial meningitis and/or septicemia on referral to hospital . This resulted in 115 verified or probable cases of MCd and 61 patient controls . Randomly drawn from three age strata, 320 population controls were actually approached and 293 (92%) of these responded to the "environmental questionnaire" . So did most of the patients (98%) . The clinical data mainly comprised information from the commencement of the disease to a sequelae check about six weeks after hospital admission . Laboratory data on strain and serum characteristics were, and still are, collected . The results are to be published in several papers . Here, some epidemiological characteristics of the material are given . Regional, seasonal, and age/sex differences in case fatality are reported and discussed.

NIPH Ann, 1983 Dec, 6(2), 151 - 3
Meningococcal disease in Norway 1980--83; Bay D et al.; The development in the epidemiological patterns of meningococcal disease in Norway after 1979 is briefly described for the general and military population . With the high incidence levels which have lasted for about nine years, the situation may be described as Norway having experienced a shift in 1974 to a new endemic level . The predicted incidence for 1983 is higher than for any year since 1941.

Can J Microbiol, 1983 Dec, 29(12), 1671 - 4
Prevention of the enhancing effect of mucin and iron in mouse meningococcal infection; Dupuy JM et al.; In vivo resistance of mice to Neisseria meningitidis was entirely abrogated by a concomitant administration of mucin and iron with N . meningitidis organisms . Resistance, however, was restored when the latter challenge was given to animals which had been immunized 7 days previously with a crude extract of meningococcal antigens (MA), BCG, or proteose peptone . These results suggest that depression or activation of the reticuloendothelial system (RES) may be important in resistant of mice to meningococcal infection . Also, like BCG, MA inoculation was able to prevent infection by Listeria monocytogenes indicating its marked ability to activate the RES . The data show that immunization can induce nonspecific RES stimulation and that the nonspecific resistance persists for at least 7 days.

Arq Neuropsiquiatr, 1983 Dec, 41(4), 343 - 55
{Neurological and cerebrospinal fluid evaluation in children with serogroup A meningococcal meningitis}; Bresolin AU; Our aim is to present the results obtained from the evaluation of the neurological examination as well as chemical and cytologic data from the CSF obtained at the admission and discharge of 255 children aged between zero and 12 years with a diagnosis of serogroup A meningococcal meningitis made at the Hospital Emilio Ribas in Sao Paulo, Brasil, in the years of 1976 and 1977 . By the time of their admission, 27 patients (10,59%) showed positive neurologic findings besides meningeal signs . Seizures were the most common ones, with higher incidence in children under 13 months; ataxia, deafness, motor deficits, neuro-psychomotor involution, subdural effusions and disturbed behavior followed in that order . Subdural effusions were found only in those under 13 months . A fatal outcome was registered in eleven (4,31%) patients, of which nine died in the first 24 hours after admission . By the time of hospital discharge 14 patients (5,49%) had neurological abnormalities, deafness and ataxia being the most common ones, in the older patients . Under 13 months, developmental involution predominated . There is no need of CSF evaluation for antibiotic therapy interruption in patients with meningococcal meningitis.

Vaccine, 1983 Dec, 1(1), 31 - 6
Physicochemical and immunological characterization of meningococcal group A polysaccharide-tetanus toxoid conjugates prepared by two methods; Beuvery EC et al.; Two methods have been applied for the covalent binding of high molecular weight Neisseria meningitidis group A polysaccharide to tetanus toxoid . The first method used cyanogen bromide as the coupling reagent and the second used both glycine and 6-amino-n-hexanoic acid as spacers and N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide as the coupling reagent . Each conjugation was performed twice . The conjugates were analysed by biochemical, physicochemical and immunochemical techniques . The immunogenic activities of the conjugates were studied in mice . The IgG responses to both components of the conjugates were measured by the enzyme-linked immunosorbent assay (ELISA) . After the first dose differences in immunogenic activity of the tetanus toxoid component of the conjugates were seen, whereas after the second dose differences in activity of the polysaccharide component were observed . The second dose of all conjugates produced clear booster effects in the responses to both components . AlPO4 potentiated both the primary antibody responses and did not influence the booster effects . These data indicate that both components of the conjugates behaved as thymic-dependent immunogens . The second method of preparation resulted in conjugates with higher immunogenic activities . Significant differences in activity, however, were seen between conjugates prepared by the same method . These data indicate that the reproducibility of the method of preparation needs further consideration.

NIPH Ann, 1983 Dec, 6(2), 205 - 9
The diagnosis of meningococcal disease by culture . Some points of practical importance; Hoiby EA et al.; Meningococcal disease has been a serious problem in Norway for nearly a decade . A nation-wide study of this disease revealed that almost 40% of all cases in clinical practice remained without a microbiological diagnosis . In the hope that this situation can be improved, a brief review is given of information available in the literature concerning collection and handling of microbiological specimens from patients with possible systemic meningococcal disease.

NIPH Ann, 1983 Dec, 6(2), 191 - 201
Untreated meningococcemia in two siblings; Lindman CR et al.; In September 1982 two siblings were admitted to hospital within a few days of each other, with almost identical symptoms of meningococcemia . One of them had been discharged from hospital four days previously, fully treated to meningococcal meningitis . Two systemic meningococcal isolates and nasopharyngeal meningococci from patient No 1 were B:15:P1 . 16 strains as well as one nasopharyngeal isolate from patient No 2 . One nasopharyngeal isolate from the father was a non-encapsulated 15:P1 . 16 strain . The two systemic isolates were clearly different with respect to the class 5 outer membrane protein(s); the second closely resembled the various nasopharyngeal isolates, all of which were identical . Only the two patients mounted detectable bactericidal antibody activity as measured by using human complement . Convalescent serum from patient No 1 after the second episode was bactericidal against the first but not the second isolate . No differences among patients and parents were found by measuring opsonizing activity . The clinical picture and the laboratory results seem to indicate that both children, one after a treated meningitis episode, had benign meningococcemia which subsequently ran its course untreated and without complications.

NIPH Ann, 1983 Dec, 6(2), 139 - 49
An ELISA study of the antibody response after vaccination with a combined meningococcal group B polysaccharide and serotype 2 outer membrane protein vaccine; Rosenqvist E et al.; The antibody response of a group of adult volunteers given a combined meningococcal group B polysaccharide and serotype 2 outer membrane protein vaccine, has been studied by the ELISA technique . The antigen was an outer membrane preparation from a non-capsular strain of Neisseria meningitidis (the vaccine strain) . The vaccination was performed as a double-blind experiment where one group of 27 persons was given the vaccine and a similar group of 28 persons was given a placebo . In addition, five volunteers from the laboratory staff were given the vaccine . Two weeks after the primary vaccination, 31 of the 32 vaccinated persons demonstrated a significant increase of specific IgG antibodies . The number with significant IgA and IgM increase was 21 and 12, respectively . A booster effect after revaccination four weeks later was found in 18 persons for IgG, in 10 for IgA and in one for IgM . Twenty-five weeks after the primary vaccination the ELISA values were significantly reduced, mostly for IgM antibodies . The mean values for IgG, IgM and IgA were then 150%, 130% and 110%, respectively, of the values before vaccination . A new way of analysing the data has also been tried for IgG determination . Instead of comparing OD values, we calculate the expression: B = D/2 . In(1 + OD/A)/(1-OD/A), where A is an experimental constant and D is the serum dilution . B then becomes linearly proportional to the antibody concentration . This way of expressing the results shows the geometric mean IgG titer 25 weeks after vaccination to be three times higher for the vaccinated than for the placebo group.

NIPH Ann, 1983 Dec, 6(2), 133 - 8
Meningococcal group B vaccine trial in Norway 1981--1982 . Preliminary report of results available November 1982; Froholm LO et al.; A combined serogroup B capsular polysaccharide and serotype 2a outer membrane complex meningococcal vaccine and a placebo preparation were tested double-blindly in 55 adult, male volunteers . The vaccine gave twofold increased binding antibodies, measured by ELISA, against non-capsular outer membrane antigen in 85 per cent of those vaccinated . Bactericidal antibodies towards a meningococcal serogroup C serotype 2a strain also increased fourfold or more among 85% vaccinated . New acquisition of meningococcal carriage was associated with antibody increase in one person from the placebo group.

NIPH Ann, 1983 Dec, 6(2), 125 - 31
Serotyping of meningococci by coagglutination with monoclonal antibodies; Froholm LO et al.; Treatment of agar-grown meningococci with dilute hydrochloric acid and suspension in saline after washing gave a preparation suitable for meningococcal serotyping by staphylococcal coagglutination with monoclonal antibodies . The monoclonal antibodies available for use and attached to protein A on the staphylococci were directed against the serotype protein antigens 2a, 2b (class 2), 15 (class 3) and the subtype protein antigens P1 . 2 and P1 . 16 (class 1) . Ninety per cent of systemic strains and thirty-four per cent of a collection of carrier isolates, both from Norway late 1981/early 1982, were typable . The serotype antigen 15 alone or in combination with P1 . 16 or P1 . 16 alone were detected in about 85 per cent of the systemic strains . The quality of the whole-cell meningococcal antigen was important for the test to be easily read.

Can J Microbiol, 1983 Dec, 29(12), 1619 - 25
Dual effect of meningococcal antigens on a T cell dependent immune response; Sparkes BG; Meningococcal antigens (MA) showed adjuvant activity when administered to mice at the same time as antigen (sheep erythrocyte (SE}, by increasing the splenocyte plaque-forming response in a dose-related manner . However, when SE were given 1 day after MA administration, the subsequent plaque formation was diminished from normal in proportion to the dose of MA injected . Splenocytes taken from mice up to 5 days after MA injection actively inhibited plaque formation when mixed with splenocytes immunized with SE 4 days earlier . Two days after MA injection the nonspecific inhibition of plaque formation was mainly due to adherent spleen cells, while at 5 days nonadherent cells had acquired the inhibitory activity . It appears that it is the degree of activation of adherent cells resulting from the timing and dosage of MA which modulates the subsequent development and secretion of antibody-forming cells.

Acta Pathol Microbiol Immunol Scand {B}, 1983 Dec, 91(6), 431 - 4
Normal bactericidal capacity against Neisseria meningitidis in serum from a patient with a hemolytically inactive complement factor 8 (C8); Strate M et al.; The bactericidal capacity of serum against Neisseria meningitidis from a 27-year-old male with two episodes of meningococcal meningitis and C8 deficiency was compared to that of normal human serum (NHS) without demonstrable antibodies against Neisseria . The in vitro bactericidal capacity of the patient serum was found to be equal to that of NHS . Incubation of both sera at 56 degrees C for 30 minutes abolished the bactericidal effect . Rocket-immunoelectrophoresis analysis of molecules immunochemically identifiable as C8 revealed no consumption of these molecules in any of the sera in the bactericidal assay . No hemolytic complement activity was found in the patient serum, whereas the donor serum had normal total hemolytic complement activity with significant consumption of C8.

Bull Soc Pathol Exot Filiales, 1983 Nov, 76(5), 634 - 43
{New epidemiologic data on meningococcal meningitis in tropical Africa}; Picq JJ et al.; From recent data, the authors touch up the epidemiological features of meningococcal meningitis in tropical Africa, especially in Sudano -sahelian areas of countries included in the "Meningitis Belt".

J Infect, 1983 Nov, 7(3), 193 - 202
875 cases of bacterial meningitis: diagnostic procedures and the impact of preadmission antibiotic therapy . Part III of a three-part series; Bohr V et al.; Data on the bacteriological findings, diagnostic measures and clinical course of 875 patients with bacterial meningitis are presented . Findings from the medical records and from a follow-up questionnaire survey of 667 of these cases revealed no significant difference between patients treated with antibiotics before admission (pretreated) and those who were not treated before admission (non-pretreated) with respect to clinical condition on admission, mortality and late sequelae . Pretreatment was, however, associated with a longer duration of symptoms . Apart from cases due to Neisseria meningitidis, there were no significant differences in diagnostic findings between pretreated and non-pretreated cases . In the group of pretreated meningococcal patients, however, positive blood cultures, pleiocytosis in the cerebrospinal fluid (CSF) and positive cultures from sites other than blood and CSF were less frequent than in the non-pretreated cases.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Nov, (11), 58 - 64
{Comparative study of the reactogenicity and immunogenicity of various doses of a chemical polysaccharide meningococcal vaccine administered by syringe and jet injector}; Pavlova LI et al.; The article presents the results obtained in the comparative study of the reactogenicity and immunogenic potency of different doses of chemical polysaccharide meningococcal vaccine, type A, introduced with a syringe and a jet-injector . The preparation has been shown to possess low reactogenicity, high immunogenic potency and to produce a sufficiently pronounced intensity of postvaccinal immunity . The preparation is recommended for wide use in immunization of adults in a dose of 75 micrograms.

J Med Microbiol, 1983 Nov, 16(4), 443 - 57
Immunogenic and protective properties of meningococcal serotype 2a protein in the hen-embryo model; Ashton FE et al.; The ability of serotype 2 outer membrane protein (SP-2) of Neisseria meningitidis strain M986 serogroup B, serotype 2a (B, 2a) to stimulate antibody formation in hens and to confer protection against meningococcal challenge to embryos from immunised hens was investigated . Hens, housed with roosters, were immunised with 100 micrograms of SP-2 once a week for 5 weeks to maintain consistent levels of serum antibody during the study . Antibodies in sera of hens, yolks and plasma of 13-day-old embryos reacted in enzyme-linked immunosorbent assays and immunodiffusion with outer membrane vesicles (OMV) from serotypes 2a, 2b and 2c and most of the other prototype group B strains of N . meningitidis . Cross-reactivity of hen sera with most OMV appeared after only one injection of SP-2 . Embryos from immunised hens were protected against challenge with up to 10,000 LD50 doses of either the homologous strain M986 (B, 2a) or strain M1011 (B, 2a) . Protection was also evident against strains 614 (W135, 2a), S5896 (Y, 2c) and 2241 (C, 2a), but not against strain 78704 (C, 2a) despite strong cross-reactivity of antibody with OMV of this strain . Embryos were only partially protected against strain 78069 (B, 2b) and were fully susceptible to strain 2996 (B, 2b) . Some protection was also obtained against meningococcal strains M1080 (B, 1), M982 (B,9), S3032 (B, 12), 79001 (B, 12), 79694 (B, 15-related) but not strain 77252 (B, nontypable) . These results suggest that proteins extracted from both serotype 2a and 2b meningococci would provide the broadest protection against infection with group B, serotype 2 meningococci and that antibody, presumably directed against common peptides in the major outer membrane proteins, can prevent infection by some other disease-associated serotypes of N . meningitidis.

Infect Immun, 1983 Nov, 42(2), 599 - 604
Reactivity and immunogenicity of bivalent (AC) and tetravalent (ACW135Y) meningococcal vaccines containing O-acetyl-negative or O-acetyl-positive group C polysaccharide; Vodopija I et al.; The immunogenicity and the reactivity of two bivalent (AC) and two tetravalent (ACW135Y) meningococcal vaccines containing either the O-acetyl-positive or the O-acetyl-negative group C polysaccharide were compared in healthy adolescent and adult volunteers . The vaccines contained high-molecular-weight, purified capsular meningococcal polysaccharides and were administered subcutaneously at a dose of 50 micrograms for each polysaccharide . Reactivity was low for all vaccines, and the tetravalent vaccines were not significantly more reactive than the bivalent vaccines . Immunogenicity was measured by assay of bactericidal antibodies in pre- and postvaccination sera . More than 90% of the vaccines had at least a fourfold increase in the bactericidal antibody titer against each group of meningococcus represented in the vaccines . Addition of polysaccharide W135 and polysaccharide Y to polysaccharides A and C did not alter the immunogenicity of the latter polysaccharides . Thus, there is no evidence of antigenic competition with the tetravalent vaccine . Comparison of the antibody response to the O-acetyl-positive and the O-acetyl-negative variants of group C polysaccharide in the bivalent vaccines, as measured by both bactericidal and enzyme-linked immunosorbent assays, indicates that in adults, the two types of group C polysaccharide are similarly immunogenic.

Infect Immun, 1983 Nov, 42(2), 471 - 9
Activation of murine B lymphocytes by Neisseria meningitidis and isolated meningococcal surface antigens; Melancon J et al.; Heat-killed Neisseria meningitidis was found to be a potent mitogen for mouse splenic lymphocytes . Results obtained with different cell separation techniques indicated that the bacteria acted to selectively induce proliferation of B lymphocytes . First, partial or total depletion of T lymphocytes by treatment with various anti-T-cell antisera plus complement did not affect the ability of the remaining spleen cells to proliferate in response to N . meningitidis . Second, T lymphocytes purified by affinity chromatography through an immunoglobulin-antiimmunoglobulin-coated glass bead column were unresponsive to meningococcal stimulation, even when provided with a source of macrophages (irradiated or mitomycin C-treated spleen cells) . Finally, treatment of spleen cells with soy bean agglutinin showed that, whereas the soy bean agglutinin-positive population (B-enriched lymphocytes) was highly responsive to stimulation by N . meningitidis, the soy bean agglutinin-negative population (T-enriched lymphocytes) displayed only a background level of proliferation when exposed to the bacteria . Isolated meningococcal surface antigens such as lipopolysaccharide (LPS) and outer membranes also possessed mitogenic activity and induced proliferation of B lymphocytes in a dose-dependent manner . Both LPS and non-LPS components contributed to the mitogenicity of outer membranes since the addition of outer membrane preparations to spleen cells from the low LPS responder C3H/HeJ mouse strain gave rise to a high level of proliferative activity.

Antimicrob Agents Chemother, 1983 Nov, 24(5), 731 - 4
Effect of subminimal inhibitory concentrations of antimicrobial agents on the piliation and adherence of Neisseria meningitidis; Kristiansen BE et al.; Neisseria meningitidis is known to be highly resistant to lincomycin (minimum inhibitory concentration greater than 32 micrograms/ml) . However, during studies on meningococcal piliation, we noticed a significant reduction in the number of pili after cultivation on lincomycin-containing selective media . This observation was followed up by in vitro and in vivo studies on the relation between lincomycin and meningococcal adherence to human epithelial cells . We found a remarkable decrease in in vitro piliation and adherence after exposure to lincomycin at concentrations as low as 0.05 micrograms/ml . By giving four healthy meningococcal carriers lincomycin orally for 3 to 6 days, the possible in vivo effect of lincomycin was studied . A marked decrease in the meningococcal counts of the pharyngeal secretion was observed . One person completely lost his meningococcal strain during the observation period.

Antibiotiki, 1983 Oct, 28(10), 764 - 7
{Efficacy of penicillin therapy of meningococcal infection in children undergoing different regimes of pathogenetic therapy}; Vereshchagin IA et al.; The course of meningococcal infection and nonspecific and specific immunity in children subjected to different regimens of pathogenetic therapy were studied . It was shown that the clinico-immunological indices were more favourable in children treated with lasix as a diuretic agent . Recovery with defects was observed in 6.8 per cent of the children of this group, while in patients subjected to routine treatment the respective value amounted to 14.6 per cent . The use of lasix in combination with penicillin increased the efficacy of penicillin therapy and shortened the recovery period by 8.4 +/- 0.2 days as compared to that of routine treatment . No unfavourable effect of elevated penicillin concentrations on the lysozyme activity, blood bactericidal characteristics and composition of immunoglobulins A, M and G in the children was recorded.

Can J Microbiol, 1983 Oct, 29(10), 1323 - 30
Mouse immune response to meningococcal antigens; Micusan VV et al.; The mouse immune response against Neisseria meningitidis was studied by using an extract from group Y (Slaterus) known to contain protein antigens common to other meningococci . By using a solid-phase radioimmunoassay, high titers of specific IgM and IgG class antibodies were measured which lasted over 2 months after immunization . These antibodies cross-reacted with similar extracts from other meningococci groups . Bactericidal antibodies directed against protein antigens were also elicited after immunization and they belonged to IgM, IgG2a, and IgG2b isotypes . Cellular immunity, expressed as delayed type hypersensitivity under the conditions tested, could be detected neither in homologous nor heterologous reactions.

J Clin Microbiol, 1983 Oct, 18(4), 905 - 11
Spin membrane immunoassay for use in meningococcal serology; Vistnes AI et al.; A modified and improved spin membrane immunoassay has been developed for detecting complement-activating antibodies to Neisseria meningitidis capsular polysaccharide antigens . The polysaccharides were incorporated in the membranes of large unilamellar vesicles prepared by the reverse-phase evaporation method and filled with the water-soluble spin label tempocholine chloride . Upon addition of group-specific antisera and complement, the lipid membrane was damaged and the spin label leaked out . This process was monitored by electron spin resonance spectroscopy . A satisfactory assay was developed for polysaccharides of group A and C, whereas in the case of the B system the assay was more labile . The method is rapid and has a sensitivity comparable to that of radioimmunoassay . When studying paired sera from five recruits vaccinated with an A + C polysaccharide vaccine, significant rises in titers to both A and C polysaccharides were observed in all the postvaccination sera.

An Esp Pediatr, 1983 Oct, 19(4), 268 - 78
{Pi phenotypes of alpha-1-antitrypsin and antiproteases in meningococcal sepsis}; Ruiz C et al.; Values of mean antiproteases were studied in 60 children with meningococcal sepsis . At illness onset, increased levels of alpha-1 antiquimotrypsin (p less than 0.001) and decreased of alpha-2 macroglobulin (p less than 0.001) were found . Moreover, patients who were complicated with a disseminated intravascular coagulation (DIC) also showed a decrease of antithrombin III (p less than 0.001) and inter alpha-1 trypsin inhibitor (p less than 0.001) . There was not relationship between antiproteases levels and mortality . In 33 cases the measures were repeated 24 hours later, but no homogeneous results were found, in spite of alpha-2 macroglobulin fall in patients complicated with DIC (p less than 0.05) . Phenotypic variants of alpha-1 antitrypsin were studied in 47 cases by isoelectric focusing . Results did not provide evidence that "abnormal phenotypes" (no-Pi MM) could facilitate meningococcal sepsis or DIC, but an increased number of "abnormal phenotypes" (5/9) were found in dead patients (p less than 0.025).

Carbohydr Res, 1983 Sep 16, 121, 233 - 41
The structure of an R-type oligosaccharide core obtained from some lipopolysaccharides of Neisseria meningitidis; Jennings HJ et al.; The main structure of a lipopolysaccharide R-type core oligosaccharide common to a number of different strains of Neisseria meningitidis has been elucidated . Methylation analysis, specific degradations, and nuclear magnetic resonance spectroscopic analysis of the dephosphorylated cores indicated that they all have the following structure . (formula see text) The determinants responsible for the L3, L7, and L9 meningococcal lipopolysaccharide serotypes are situated in this oligosaccharide.

Clin Immunol Immunopathol, 1983 Sep, 28(3), 413 - 7
Meningococcal meningitis in a women with inherited deficiency of the ninth component of complement; Fine DP et al.; A 17-year-old woman presented with acute pyogenic meningitis; Neisseria meningitidis group C was isolated from blood on culture . Complement assays demonstrated a hemolytic complement titer of 12 u/ml; individual components were normal except for C9, which was absent by both functional and antigenic analysis . Family studies were consistent with a familial C9 deficiency, autosomal co-dominant inheritance . This is the first report of the association of C9 deficiency and disseminated neisserial infection; whether this complement deficiency predisposes to the neisserial infection remains to be established.

Am J Clin Pathol, 1983 Sep, 80(3), 386 - 7
Bacterial meningitis . Effect of antibiotic treatment on cerebrospinal fluid; Blazer S et al.; The effects of full short-term antibiotic treatment on cerebrospinal fluid (CSF) findings were studied retrospectively in 68 children with acute bacterial meningitis . The features of CSF at admission were compared with those of the CSF obtained after 44-68 hours of therapy . Except in one case with H . influenzae and one case with pneumococcal meningitis, all CSF cultures were negative in the repeat specimen . In three of 16 children with meningococcal meningitis, the CSF glucose levels became normal in the second specimen . In all remaining 65 children, however, full intravenous antibiotic treatment for 44-68 hours did not alter the biochemistry and cytology of the CSF, which retained its "bacterial" character . From these findings it may be discerned that partial antibiotic treatment is even less likely to distort a 'bacterial' CSF.

An Esp Pediatr, 1983 Sep, 19 Suppl 18, 27 - 35
{Advances in the treatment of endotoxic shock}; Rodriguez Lopez R et al.; Authors present their adopted measures, in the different clinical stages of endotoxic shock with a phisiological approach, paying special attention to those secondary to meningococcal infections.

Rev Infect Dis, 1983 Sep-Oct, 5 Suppl 4, S708 - 14
Mechanisms of mucosal invasion by pathogenic Neisseria; McGee ZA et al.; Neisseria gonorrhoeae are transported across the mucosa of human fallopian tubes in organ culture by mucosal cells . The steps in this process are (1) attachment of gonococci to microvilli of nonciliated cells, (2) phagocytosis of gonococci by these cells, (3) transport of phagocytic vacuoles containing gonococci to the base of the cell, and (4) exocytosis of gonococci with phagocytic vacuoles into the subepithelial tissues . In vivo gonococci in the subepithelial tissues may cause extensive local disease (e.g., salpingitis) or invade blood vessels to cause disseminated disease . Preliminary studies of human nasopharyngeal tissue in organ culture infected with Neisseria meningitidis indicate that meningococci attach to microvilli of nonciliated cells and are phagocytized by these cells . They subsequently appear in subepithelial tissues, but the route they take is not yet certain . These observations suggest that the mechanisms of attachment to and penetration of fallopian tube and nasopharyngeal mucosa by N . gonorrhoeae and N . meningitidis are similar or possibly identical.

J Infect Dis, 1983 Sep, 148(3), 369 - 76
Interaction of Neisseria meningitidis with human nasopharyngeal mucosa: attachment and entry into columnar epithelial cells; Stephens DS et al.; The mechanisms by which Neisseria meningitidis establishes a carrier state or invades mucosal surfaces of the host to cause septicemia and meningitis are unknown . An experimental model of human columnar nasopharyngeal tissue in organ culture was developed, and the interaction of encapsulated, piliated N meningitidis with this mucosal surface was studied . Electron microscopic studies showed that meningococci attached selectively to nonciliated columnar cells of the nasopharynx . After attachment, the microvilli of these nonciliated cells elongated and surrounded the organisms . Six to twelve hours after infection, endocytic vacuoles containing meningococci were seen in the apical portion of some nonciliated columnar cells . Later, diplococci were seen in the subepithelial tissues adjacent to lymphoid tissue; this observation suggested that meningococci had penetrated the epithelial layer . The interaction of meningococci with the nasopharyngeal epithelium may be an important means whereby these bacteria establish a carrier state or invade the host.

Clin Pediatr (Phila), 1983 Sep, 22(9), 605 - 7
Relapsing Neisseria meningitidis infection associated with C8 deficiency; Liston TE; Infection due to serogroup Y of Neisseria meningitidis has many clinical manifestations, ranging from mild bacteremia to fatal sepsis and meningitis . N . meningitidis infection may coincide with several complement deficiencies . A child is described who suffered from recurrent disease due to N . meningitidis, group Y, attributed to deficiency of the eighth component of complement (C8) . In a review of the literature, recurrent infection occurred in six of 13 children with complement deficiency, four of whom had serotyping positive for N . meningitidis, group Y . Screening for complement deficiency is recommended for all children with meningococcal disease due to N . meningitidis, group Y, and for any child with recurrent infection due to any Neisseria species.

Diagn Microbiol Infect Dis, 1983 Sep, 1(3), 185 - 92
Correlation of E . coli K-1 bacteremia and capsular polysaccharide antigenemia in acute and chronic infection; Stevens P et al.; The K-1 polysaccharide is an important virulence factor in human E . coli infections . Using E . coli 016K1, we investigated the kinetic association of bacteremia and K-1 antigenemia in acute lapine and canine infections and in a chronic infection model of neutropenic rats . Additionally, we assessed the presence of K-1 antigenemia in E . coli K-1 bacteremic patients . K-1 was measured by a solid phase radioimmunoassay (RIA) using cross-reactive equine anti-Group B meningococcal IgM . In acute infections, none of the dogs or rabbits developed antigenemia even with a bacteremia of 2 X 10(4) CFU/ml or 5 X 10(5) CFU/ml, respectively . Antigenemia appeared in the rabbit only with an infecting dose of greater than or equal to 5 X 10(8) CFU . In the rat model we observed an initial bacteremia of 10(3) CFU/ml, which increased to 10(6) CFU/ml at 24 hrs . However, antigenemia was most often delayed, appearing in only greater than or equal to 30 hrs postinfection . Percent mortality was directly associated with the degree of bacteremia and antigenemia . In acute human E . coli K-1 bacteremia, 11 of 22 (50%) of patients were positive for K-1 antigenemia . The data demonstrated that K-1 polysaccharide was not usually detectable in the early stages of bacteremia, but occurred only after prolonged infection or very high infecting doses . The RIA to measure K-1 antigenemia would not be a useful diagnostic tool.

J Gen Microbiol, 1983 Sep, 129 (Pt 9), 2761 - 8
Antigenic cross-reactivity of Neisseria pili: investigations with type- and species-specific monoclonal antibodies; Virji M et al.; Monoclonal antibodies have been produced with both type-specific and broadly cross-reacting properties against the variant pili of Neisseria gonorrhoeae P9 . Competitive radioimmunoassays demonstrated that at least three separate epitopes contribute to type-specificity within the strain . ELISA using purified pili from clinical isolates showed that some of the type-specific epitopes are randomly distributed among variants of single strains isolated from different sites in sexual partners . Cross-reacting antibody SM1 recognized an epitope present on all gonococcal isolates . This epitope was also present on a large proportion of meningococci and could be directly demonstrated in CSF from a patient with meningococcal meningitis . Commensal Neisseria and other Gram-negative bacteria tested failed to react . The meningococci which lack the epitope recognized by the antibody SM1 were nevertheless shown by electron microscopy to be pilated, suggesting that pili from meningococci may be antigenically more diverse than those from gonococci.

Lancet, 1983 Aug 13, 2(8346), 355 - 7
Antigenic similarities between brain components and bacteria causing meningitis . Implications for vaccine development and pathogenesis; Finne J et al.; Glycopeptides containing polysialic acid units were isolated from human and rat brain and tested for reactivity with antibodies against meningococcal capsules . The polysialosyl glycopeptides bound specifically to horse antiserum against meningococcus group B . The interaction was inhibited by capsular polysaccharides from meningococcus group B but not groups A or C . The capsular polysaccharide of Escherichia coli K1, which is immunochemically similar to the group B polysaccharide, also inhibited binding . These findings could explain the failure to develop efficient vaccines against group B meningococcus or E coli K1 and also suggest that immunological tolerance could be a factor in the pathogenesis of meningitis caused by these bacteria . The presence of the cross-reactive brain component calls for caution in efforts to develop capsular polysaccharide vaccines from these bacteria or the proposed use of passively administered antibodies as immunotherapy of neonatal meningitis.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Aug, (8), 41 - 5
{Surface antigen structure of Neisseria meningitidis . I . The isolation of a serotypic antigenic complex of N . meningitidis strain B16B6 by direct detergent treatment and its immunochemical characteristics}; Gorshkova VI et al.; The method for obtaining a serotyping antigenic complex from N . meningitidis B16B6 by their direct treatment with the mixture of detergents (0.5% sodium desoxycholate and 0,5% cholic acid in the proportion 1 : 1) in 0.5 M KCl solution is proposed . Such treatment has been found to increase the yield of the preparation in terms of protein more than 4 times in comparison with earlier methods for obtaining serotyping antigens . The immunochemical study of the preparation has demonstrated its serological specificity and high immunological activity, not inferior to that of serotyping antigenic preparations from group B meningococci, obtained by the heretofore known methods.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Aug, (8), 38 - 41
{Electron microscopic study of meningococci in stab cultures}; Reshilov LN et al.; The study of the ultrastructure of meningococci (strain C0638) in the process of submerged batch cultivation permitted the authors to follow changes in the fine structure of these microorganisms in different phases of the growth of the culture . Thus, the meningococcal populations retained their ultrastructure most intact during the exponential phase and the growth rate deceleration phase . During these growth phases a faintly pronounced reaction of the surface structures with ruthenium red was observed . In the stationary phase and in the atrophy phase this reaction was completely absent . The accumulation of exotoxin bubbles in the membrane was shown to achieve its maximum in the atrophy phase; besides, these structures regularly appeared at the death of the cells under the action of alkali . A hypothesis explaining the appearance of these bubbles is put forward.

J Gen Microbiol, 1983 Aug, 129 (Pt 8), 2451 - 6
Immunological properties of monoclonal antibodies specific for meningococcal polysaccharides: the protective capacity of IgM antibodies specific for polysaccharide group B; Moreno C et al.; Two IgM monoclonal antibodies, MB32 and MB34 specific for meningococcal polysaccharide group B have been raised . Both were detectable by radioimmunoassay and agglutination, but only MB34 was effective in counter immunoelectrophoresis and complement fixation . MB34 was also far more potent than MB32 when tested for passive protection of mice infected with either Neisseria meningitidis group B or Escherichia coli K1 . These data demonstrate that group B-specific antibodies do play a protective role in mice infected with these bacteria.

J Infect Dis, 1983 Aug, 148(2), 249 - 53
Serotypes and polyacrylamide gel electrophoresis types among disease-associated isolates of group B Neisseria meningitidis in Spain, 1976-1979; Mocca LF et al.; A high annual incidence of meningococcal meningitis and septicemia occurred in Spain from 1976 through 1980 with a peak of 19 cases per 100,000 population in 1979 . Approximately 80% were caused by group B Neisseria meningitidis . Studies were undertaken to determine the distribution of groups, outer membrane protein serotypes and polyacrylamide gel electrophoresis (PAGE) types among 338 disease-associated group B isolates from six regions of Spain . The related serotypes 1, 8, and 15 accounted for 38% (129 of 338) of the isolates . Serotype 2, the major disease type in the United States, was responsible for 14% (48 of 338) of the disease in Spain and was prevalent in only one region . Forty-three percent (146 of 338) were nonserotypable . The predominant PAGE type among the nonserotypable strains was PAGE type IV (79%) . These studies demonstrate the necessity of surveillance for selection of suitable serotypes to be included in protective group B meningococcal vaccines.

Infect Immun, 1983 Aug, 41(2), 609 - 17
Immunological evaluation of meningococcal group C polysaccharide-tetanus toxoid conjugate in mice; Beuvery EC et al.; Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugate was prepared to obtain the polysaccharide component in a thymus-dependent form and to preserve the immunogenic properties of the tetanus toxoid component . Biochemical and immunochemical analyses of this conjugate revealed that (i) it was composed of equal amounts of polysaccharide and protein; (ii) the antigenic activity of the polysaccharide component was greatly reduced; (iii) it contained about 10% free polysaccharide; (iv) the composition was not homogeneous; and (v) only 5% of the tetanus toxoid component was present at the surface of the conjugate molecules . In this study, the influence of these characteristics on the antibody response to both components in mice was investigated . The dose-response relationship, the persistence of antibodies, a possible antigenic competition, and the specificities of the antibodies induced were also studied . Our data suggest that the conjugate behaves as a pronounced thymus-dependent antigen, that the tetanus toxoid component is more immunogenic at lower dosages (0.8 and 20 ng) than equivalent doses of tetanus vaccine, that the presence of free polysaccharide does not influence the induction of antibodies to polysaccharide by the conjugate, and that no antibodies to new structures in the conjugate are induced . These characteristics favor the application of this conjugate as a vaccine for human use.

Br J Vener Dis, 1983 Aug, 59(4), 228 - 31
Neisserial colonisation of the pharynx; Young H et al.; The spectrum of neisserial colonisation of the pharynx was determined from 3557 throat exudates cultured on modified New York City (MNYC) medium . Oxidase positive Gram-negative diplococci (GNDC) were isolated from 1204 (33.8%) of the throat cultures . Neisseria gonorrhoeae, N meningitidis, and N lactamica accounted for 20.3%, 74.2%, and 3.7% of the oxidase positive GNDC respectively . The observed coexistence of gonococci and meningococci in the pharynx (0.39%) was significantly different (p less than 0.001) from the theoretical expected value (1.7%) . The prevalence of pharyngeal infection in patients with gonorrhoea was 4.3% for all men, 11% for homosexual men, and 7.9% for women . Despite the risks of disseminated infection and spread to sexual partners, the detection of pharyngeal gonorrhoea is less important than that of endocervical infection in women, urethral infection in heterosexual men, and anorectal infection in homosexual men.

Ann Intern Med, 1983 Jul, 99(1), 35 - 8
Absence of the seventh component of complement in a patient with chronic meningococcemia presenting as vasculitis; Adams EM et al.; A previously healthy 40-year-old man presenting with fever, arthritis, and cutaneous vasculitis was found to have chronic meningococcemia . Evaluation of his complement system showed an absence of functional and antigenic C7, compatible with a complete deficiency of the seventh component of complement . Study of the patient's family spanning four generations showed heterozygous deficiency of C7 in five members . Chronic neisserial infection can be associated with C7 deficiency and must be distinguished from other causes of cutaneous vasculitis.

J Infect, 1983 Jul, 7(1), 39 - 45
Meningococcal meningitis in childhood . A five-year study of meningococcal meningitis in Ibadan, southern Nigeria; Nottidge VA; Meningococcal meningitis is uncommon in the rain belt of southern Nigeria . Only twenty-six children were treated in one hospital in five years . Almost half the total number were seen during the four dry months of the year . However, the incidence in any one year was not necessarily correlated with the season . It appears that the longer the disease lasted before admission, the better the prognosis . Also, if the disease was severe enough to require admission within 24 hours of onset, the prognosis was poor . Survivors did not develop complications.

Rev Infect Dis, 1983 Jul-Aug, 5 Suppl 3, S451 - 8
Rifampin and minocycline in meningococcal disease; Beaty HN; Military recruits in four companies were given minocycline, rifampin, ampicillin, or placebo for five days . All antibiotics reduced the rate of carriage of Neisseria meningitidis during treatment, but the effect was significantly more prolonged with minocycline and rifampin . The only difference between these two drugs lay in the isolation of rifampin-resistant meningococci from 17 recruits who received that antibiotic . No isolates were found to be resistant to minocycline . During an outbreak of meningococcal disease among military recruits, minocycline (100 mg every 12 hr) was administered to 8,721 trainees for five days . No new cases of meningococcal disease occurred for the next four weeks . Six new cases then developed among recruits who had begun their training after the initial course of treatment . A second cycle of minocycline, followed in one week by administration of group C polysaccharide vaccine, terminated the outbreak.

Biull Eksp Biol Med, 1983 Jul, 96(7), 29 - 31
{Study of platelet function by quantitative determination of the fluorescence intensity of 5HT-organelles}; Astrina OS et al.; 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.

Infect Immun, 1983 Jul, 41(1), 54 - 60
Cloning and analysis of the K1 capsule biosynthesis genes of Escherichia coli: lack of homology with Neisseria meningitidis group B DNA sequences; Echarti C et al.; Genes coding for production of the K1 polysaccharide capsule of Escherichia coli have been cloned . Complementation, insertion, and deletion analyses were used to localize the K1 genes and demonstrated that a minimum of 9 kilobases of DNA split into at least two gene blocks is involved in synthesis and assembly of the capsule . One of the gene blocks is responsible for biosynthesis of the polysaccharide, and the other is responsible for extracellular appearance of capsular material . Using cloned K1 genes as probes in Southern blot experiments, we detected homology to DNA from strains of E . coli capsular types K92, K7, and K100 . In contrast, no homology was apparent between K1 genes and DNA from meningococcus group B, although the K1 and group B capsules are chemically and immunologically identical.

Infection, 1983 Jul-Aug, 11(4), 192 - 5
Quantitation of endotoxin in blood from patients with meningococcal disease using a limulus lysate test in combination with chromogenic substrate; Harthug S et al.; The levels of endotoxin in blood were determined using the Limulus lysate test in combination with a chromogenic substrate . Plasma was analyzed from four patients with fatal meningococcal septicaemia and from one patient who survived meningococcal meningitis . All septicaemia patients showed high levels of endotoxin in their blood during the early stage of their disease . In two of these patients, blood samples collected at intervals of two days revealed a gradual disappearance of measurable endotoxin from the circulation . The patient with meningitis had no clinical signs of circulatory deficiency or coagulopathy and was consistently negative for endotoxin using this test procedure . Pretreating the plasma with heat and alkali and combining the Limulus lysate test with a chromogenic substrate seem to provide a sensible method for the detection and quantitation of endotoxin in blood.

J Biol Stand, 1983 Jul, 11(3), 195 - 204
The enzyme-linked immunosorbent assay of meningococcal and some related Escherichia coli polysaccharides; Beuvery EC et al.; A non-competitive enzyme-linked immunosorbent assay (ELISA) system has been developed for the quantitative, sensitive and specific determination of meningococcal polysaccharides . A prerequisite, however, is the correspondence of the O-acetyl content and the molecular size of the polysaccharides in the samples and the reference preparation . If these characteristics differ, special precautions in the use of antibodies to both the O-acetylated and the non-O-acetylated variants have to be taken, including the testing of the sample in at no less than three dilutions.

Ann Emerg Med, 1983 Jun, 12(6), 391 - 3
Complete heart block in meningococcemia; Detsky AS et al.; A 41-year-old man died of meningococcemia after presenting with skin rash, fever, and bradycardia . Electrocardiograms demonstrated intermittent complete heart block, and necropsy showed myocarditis with focal necrosis of the conduction system . This syndrome should be recognized as typical for meningococcemia, and all patients with meningococcal disease should be observed carefully for the development of bradycardia.

J Immunol, 1983 Jun, 130(6), 2882 - 5
IgA blocks IgM and IgG-initiated immune lysis by separate molecular mechanisms; Griffiss JM et al.; Circulating IgA which does not bind the first component of complement (C) and does not activate the classical C pathway, blocks the initiation of C-mediated immune effector mechanisms . In at least two clinical situations, epidemic meningococcal disease and severe hepatic dysfunction, IgA blockade of one such mechanism, immune lysis, results in susceptibility to hematogenous bacterial dissemination . The presence of strain-specific IgM, but not IgG, in the sera of susceptibles at the time of dissemination suggested that IgA blockade of IgM-initiated lysis involves a separate mechanism more sensitive to quantitative changes than that involved in IgA blockade of IgG-initiated lysis . We report here that whereas IgA blockade of IgG-initiated immune lysis is a competitive function of the ratio of IgA to IgG, the blocking of IgM-initiated lysis is a noncompetitive function of the ratio of IgA to target cells, independent of the concentration of IgM . In the presence of sufficient IgA to saturate binding sites, IgM is an impotent bystander unable to compete for sites or initiate lysis . Therefore, C-mediated effector mechanisms are more sensitive to quantitative changes in circulating IgA and target cells (binding sites) in the absence of IgG than in its presence . Neither mechanism appears related to binding kinetics.

NIPH Ann, 1983 Jun, 6(1), 85 - 90
Sequelae of meningococcal disease - studied about six weeks after hospital admission; Djupesland G et al.; As part of a greater project (MenOPP), the type, distribution and frequency of sequelae after meningococcal disease (MCd) were estimated on the basis of examinations carried out about six weeks after hospital admission . Well documented sequelae were found in about 18% of 102 MCd cases compared to about 3% in 61 control patients . In 18 control patients with meningitis/septicemia due to other bacteria, the sequelae frequency was 11% . Our MCd sequelae results correspond with many of those published during the last few years . The frequency of uncertain sequelae was about the same (16%) in the MCd and the control group patients . A routine examination six weeks and one year after a MCd episode seems to be useful for the individual patient and for the research on better prophylaxis and improved treatment.

NIPH Ann, 1983 Jun, 6(1), 49 - 53
Pathogenesis of hemorrhagic skin lesions in meningococcal disease; Dahle JS; The pathogenesis of purpuric skin lesions in meningococcaemia is still not clear . The histopathology of biopsy specimens from human purpura resembles that of the local Shwartzman reaction in rabbits . However, the early histopathological picture of purpuric lesions shows a resemblance to the experimental epinephrine-endotoxic reaction produced in rabbits . Furthermore, immunological reactions may play an important role in the pathogenesis since deposits of immunoglobulins, complement and fibrinogen can be demonstrated in the walls of capillaries and small vessels in the dermis of patients with acute meningococcaemia.

NIPH Ann, 1983 Jun, 6(1), 75 - 84
Some agent characteristics and their coexistence related to occurrence and severity of systemic meningococcal disease in Norway, Winter 1981-1982; Bovre K et al.; Characteristics of 67 strains of Neisseria meningitidis causing systemic disease in Norway during the winter 1981-82 are reported and related to clinical manifestations . Included in the study were also pharyngeal isolates of meningococci collected in the same period from 35 healthy military recruits . The strains were examined for serogroup, serotype as determined with monoclonal antisera (against antigens 2a, 2b, 12, 15 and 16), and sulfonamide susceptibility . Predominating in the systemic disease material were serogroup B, serotype 15, 16 (or 15), and sulfonamide-resistant strains . This complex of characteristics also appeared to be associated with the severity of manifestations (septicemia and death) . The material of meningococci from healthy carriers unassociated with cases of disease was clearly different; these strains were typically non-groupable, non-typable and sulfonamide-sensitive . The full combination of traits usually seen in strains causing systemic disease was rare in carrier isolates . The results are discussed in relation to the epidemiological development of meningococcal disease in Norway.

NIPH Ann, 1983 Jun, 6(1), 65 - 73
Surface polysaccharide of Moraxella non-liquefaciens identical to Neisseria meningitidis group B capsular polysaccharide . A chemical and immunological investigation; Bovre K et al.; In whole cell preparations of 27 nonmucoid strains of Moraxella nonliquefaciens neuraminic acid was detected by gas chromatography (GC) in 16 (59%) of the strains . Seven neuraminic-acid-containing strains were tested for agglutination with diagnostic group-specific meningococcal antisera produced in rabbits, and all were positive with group B serum . Counter-immunoelectrophoresis of bacterial suspensions of the three strains with the strongest reaction with such anti-group B serum gave distinct precipitation lines . When tested by double immunodiffusion in agarose with monoclonal antibody to meningococcal group B polysaccharide, suspension of a strain of M nonliquefaciens gave identity reaction with a strain of Neisseria meningitidis, and reacted even more strongly than the latter . Phenol extracts of M nonliquefaciens strains generally contained higher amounts of neuraminic acid than N meningitidis group B strains . Neuraminic-acid-containing polysaccharides of M nonliquefaciens strains sedimented more slowly by ultra-centrifugation than the group-specific B polysaccharide of N meningitidis strains . They also reacted more strongly with a monoclonal anti-group B antiserum than did N meningitidis group B capsular polysaccharide in an antibody binding inhibition test (solid phase radioimmunoassay) . Immunological reactivity of the polysaccharides of both species was lost if extraction was performed with unbuffered phenol at 68 degrees C, instead of with neutral phenol at 4 degrees C . The results show that several strains of M nonliquefaciens, often inhabiting the human nose, have high levels of a surface polysaccharide chemically and immunologically closely similar to N meningitidis group B capsular polysaccharide . The cross-reactivity may have immunological implications for meningococcal disease.

NIPH Ann, 1983 Jun, 6(1), 59 - 63
Unusual manifestations of meningococcal infection . A review; Odegaard A; Unusual manifestations of meningococcal infection as pneumonia, pericarditis, endocarditis, arthritis, urogenital infections and acute abdominal disease are seen combined with meningitis or septicemia, but can also appear alone without systemic disease . Incidence, diagnosis, clinical symptoms and therapy are briefly discussed with documentation from literature.

NIPH Ann, 1983 Jun, 6(1), 55 - 7
Primary meningococcal conjunctivitis followed by meningitis and septicemia; Odegaard A; One case of meningococcal conjunctivitis followed by meningitis and septicemia with fatal outcome is described . Primary meningococcal conjunctivitis is rare, but 10% of the published cases are complicated by systemic infection . It is recommended that these patients be given both local and parenteral treatment . The value of culturing the purulent exudate from the conjunctival sac to reach an etiological diagnosis is pointed out.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Jun, (6), 91 - 4
{Comparative evaluation of different meningococcal group-specific erythrocyte diagnostic kits in passive hemagglutination test}; Tumanian AA et al.; The comparative evaluation of the sensitivity and specificity of serogroup A, C, Y meningococcal antigenic preparations obtained by different methods was carried out by means of the passive hemagglutination test . In case of group 0 (I) human red blood cells sensitized with serogroup A and C vaccinal preparations obtained by Gotschlich's method (designated as A-1 and C-1) were used . In the other case formalin-treated sheep red blood cells sensitized with group-specific polysaccharides obtained by alcohol precipitation from the cultural fluid of group A, C and Y meningococci with subsequent heating (designated as A-2, C-2, Y) were used . Titrations with commercial immune rabbit sera showed that both variants of the antigenic preparations were similar in their specificity and sensitivity . In patients with the symptoms of meningitis the diagnostic titer was 1:40 for preparations A-1, C-1 and 1:80 for preparations A-2, C-2 and Y . The results of the examination of 164 patients (220 serum specimens) demonstrated that these preparations were of equal diagnostic value.

Pediatrics, 1983 Jun, 71(6), 923 - 6
Influence of age on serogroup distribution of endemic meningococcal disease; Baker CJ et al.; The age distribution of 126 infants and children with disseminated meningococcal disease hospitalized consecutively in Houston between January 1977 and June 1979, and between January 1981 and June 1981 was analyzed and compared with that in the United States as a whole and to that during outbreaks of group B disease in North America and epidemics of group C disease in South America . Eighty-one (64.3%) isolates from Houston cases were serogroup B and 37 (29.4%) were serogroup C Neisseria meningitidis . Children with serogroup C disease were significantly older than those with group B disease (P = .017) . Of the children with serogroup B infections, 33% were less than 12 months of age and 8.6% were less than 3 months of age . Of those with serogroup C disease, only 2.7% were less than 3 months of age and the majority (73%) were more than 2 years of age . These age distributions are similar to those reported for the entire United States during endemic periods . In contrast, focal outbreaks of group B meningococcal infection occurred in populations that were significantly older (0.02 greater than P less than .05) . Similarly, epidemic disease in South America due to serogroup C strains also occurred in older children when compared with the occurrence of endemic group C disease in the United States (P = .02).

NIPH Ann, 1983 Jun, 6(1), 43 - 7
Heparin for infants and children with meningococcal septicemia . Results of a randomized therapeutic trial; Haneberg B et al.; Heparin has been given intravenously, as part of a prospective study, to 11 of 26 infants and children with severe meningococcal septicemia . This therapy was started as early as possible following admission to hospital, and continued for two days . The age and sex distributions were roughly similar for the two treatment groups, but the prognostic signs on admission were somewhat less favourable for the group that did not receive heparin . Two boys who received heparin and two girls who did not, died . The clinical courses of the surviving patients in the two groups were also roughly similar, except that the tendency to cutaneous necroses was slightly more prominent in those who had not received heparin . We have thus no evidence that heparin has any great influence on the final outcome of meningococcal septicemia, even when given so early that shock had not developed.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Jun, (6), 67 - 9
{The role of the population gene pool in meningococcal infection morbidity}; Petrunin IuP et al.; The character of the distribution of HLA antigens in patients with meningococcal infection among Russians and Touvinians was revealed . The markers of susceptibility to meningococcal infection were detected in each national group . These markers were HLA-Bw22 in Touvinians . The gene of susceptibility to meningococcal infection occurred among Touvinians 2.3 times more frequently . This was probably the cause of a higher morbidity rate in meningococcal infection among Touvinians than among Russians.

Zh Mikrobiol Epidemiol Immunobiol, 1983 May, (5), 50 - 4
{Biological properties and serological types and groups of pneumococci isolated from suppurative meningitis patients}; Demina AA et al.; The results of the study of the biological and serological properties of pneumococci isolated from the cerebrospinal fluid and the blood of patients with purulent meningitides are presented . Serological types were determined in 64 pneumococcal strains . They were found to belong to 16 known serological types and groups; of these, 10 had been included into the existing 14-component polysaccharide capsular pneumococcal vaccine . Serotypes 1, 19, 6, 12 and 20 were most frequently isolated from patients irrespective of their age; from children meningococci of serotype 12 were most frequently isolated . In lethal cases types 1, 19 and 2 were isolated from adults and type 12, from children . At the moment of isolation pneumococci possessed biological characteristics typical of this species.

Monatsschr Kinderheilkd, 1983 May, 131(5), 277 - 81
{Cardiac complications in meningococcal infections}; Fegeler U et al.; The clinical courses of three children with meningococcal meningitis and cardiac complications are described . In two patients a mixed peri/myocardial form of cardiac involvement is probable . One child showed a pericarditis with relapses as found in the postpericardiotomy syndrome . The pathogenesis of the cardiac involvement in meningococcal infections is discussed based on the literature . The three cases observed are tentatively classified accordingly.

South Med J, 1983 May, 76(5), 567 - 70
Ataxia in Listeria monocytogenes infections of the central nervous system; Bowie D et al.; From 1976 to 1981 Listeria monocytogenes was second only to Neisseria meningitidis as the cause of bacterial infections of the central nervous system in adults at our hospital . None of the patients with Listeria infection was immunosuppressed or had an underlying malignancy . Ataxia was an initial feature in five of the eight patients, and in three of them it persisted beyond their discharge from the hospital . Ataxia was not a feature of the clinical picture of 14 other adult patients with meningococcal and pneumococcal meningitis . Our data indicate that L monocytogenes should be suspected as the etiologic agent in an adult with ataxia and infection of the central nervous system.

J Infect, 1983 May, 6(3), 247 - 55
Vaccine potential of meningococcal group C polysaccharide-tetanus toxoid conjugate; Beuvery EC et al.; The antibody response in mice to Neisseria meningitidis (meningococcal) group C polysaccharide could be modified by its conjugation to proteins, i.e . tetanus toxoid . Whereas the pure polysaccharide behaved as a T-independent antigen, the polysaccharide-protein conjugate was clearly a T-dependent antigen, as shown by the pronounced IgG response after the first dose and by the booster effect after the second dose . In comparison, group C polysaccharide-outer membrane protein complexes isolated from the cell-free culture liquid of a meningococcal culture induced only a low level of IgG antibodies . Conjugation did not result in a reversion of tetanus toxoid to toxin . Tetanus toxoid present in the conjugate was as immunogenic as tetanus vaccine.

Zh Mikrobiol Epidemiol Immunobiol, 1983 May, (5), 81 - 4
{Safety and reactogenicity of a group-A meningoccal polysaccharide vaccine for children 5 to 14}; Chernyshova TF et al.; The safety and reactogenicity of group A meningococcal polysaccharide vaccine prepared at the G . N . Gabrichevsky Research Institute for Epidemiology and Microbiology (Moscow) and intended for the immunization of children aged 5-14 years were studied . The data obtained in this study made it possible to characterize the preparation as safe and mildly reactogenic . Shifts in the blood formula registered 24 hours after the injection of the vaccine remained within the limits of physiological fluctuations . Subfebrile temperature persisting for 2 days was registered in some of the children aged 5-8 years . Local reaction in the form of hyperemia at the site of injection was insignificant . The optimum vaccination dose will be determined on the basis of the whole complex of the data presented in this work, as well as the data on the immunological activity of the preparation.

J Clin Microbiol, 1983 May, 17(5), 722 - 7
A new serogroup (L) of Neisseria meningitidis; Ashton FE et al.; A strain of neisseria meningitidis (LCDC 78189) isolated from the mother of a 3-year-old male with meningococcal meningitis was found to be antigenically distinct from the known serogroups A, B, C, D, H, I, K, X, Y, Z, 29E, and W135; it was designated serogroup L . Anti-78189 serum specifically agglutinated the homologous strain and three other strains which were isolated from the father and two other contacts of the child . Only those strains isolated from the contacts produced immunoprecipitates with the anti-78189 serum by the antiserum-agar method . A structurally unique capsular polysaccharide which was obtained from strain 78189 in a highly purified state was demonstrated to be the antigen responsible for the serological properties of the strain . The polysaccharide formed a precipitin band with the anti-78189 serum but not with the meningococcal grouping sera, and it was also able to absorb both the agglutinating and precipitating activity from the anti-78189 serum.

J Bacteriol, 1983 May, 154(2), 728 - 36
Physiology of sialic acid capsular polysaccharide synthesis in serogroup B Neisseria meningitidis; Masson L et al.; The pathway for biosynthesis of sialic acid capsular polysaccharide was examined in Neisseria meningitidis serogroup B strain M986 and in strain PRM102, an isogenic mutant defective in polysaccharide production . Strain PRM102 was found to possess only 25% of the level of sialyltransferase activity that was found in strain M986, but it had wild-type levels of both the N-acetylneuraminic acid (NANA) condensing enzyme and the CMP-NANA synthetase . A new meningococcal enzyme, a CMP-NANA hydrolase, was found in both meningococcal strains . This enzyme generated CMP and NANA from CMP-NANA, had a Km of 0.88 microM, had a Vmax of 10.75 nmol of NANA produced per h per mg of protein, and was completely inhibited by 45.3 microM CMP . The sialyltransferase, which also had CMP-NANA as substrate, was insensitive to CMP addition . Subcellular fractionation and purification of cytoplasmic and outer membranes on sucrose density gradients revealed that both the sialyltransferase and the CMP-NANA hydrolase were cytoplasmic membrane associated . The NANA condensing enzyme and the CMP-NANA synthetase were found to be cytosolic . A working hypothesis for the regulation of sialic acid polysaccharide synthesis was developed . The CMP-NANA hydrolase with its high affinity for CMP-NANA regulates polysaccharide formation by the sialyltransferase, whereas CMP, a product of both the sialyltransferase and the CMP-NANA hydrolase, modulates the activity of the hydrolase on the cytoplasmic membrane.

N Engl J Med, 1983 Apr 21, 308(16), 913 - 6
Prevalence of congenital or acquired complement deficiency in patients with sporadic meningocococcal disease; Ellison RT 3rd et al.; We evaluated the complement system in 20 patients presenting with a first episode of meningococcal meningitis, meningococcemia, or meningococcal pericarditis . Assays of total serum complement activity were performed prospectively in 12 patients and retrospectively in 8 . Six of the twenty patients had a complement deficiency (CH50 greater than 2 S.D . below the normal mean) . Three of these six had a deficiency of a terminal-pathway protein (C6 in two and C8 in one), and the other three had deficiencies of multiple complement proteins associated with underlying systemic lupus erythematosus or multiple myeloma . Patients with decreased amounts of complement were similar to normal patients in terms of sex, age, type of infection, and meningococcal serogroup, but 3 of the 6 patients with a complement deficiency were black, as compared with none of the 14 patients with normal function (P = 0.018) . Complement deficiency is common in patients with a first episode of meningococcal disease and may be due to either a deficiency in a single terminal protein or a complement-depleting underlying illness.

Clin Exp Immunol, 1983 Apr, 52(1), 153 - 6
Meningococcal meningitis associated with persistent hypocomplementaemia due to circulating C3 nephritic factor; Thompson RA et al.; Two teenage patients who presented with meningococcal meningitis were found to have persistently low C3 levels even after recovery . This was accompanied by circulating C3 nephritic factor, which persisted for more than 12 months in each case . Neither patient had evidence of partial lipodystrophy or of glomerulonephritis initially, although one patient subsequently developed mesangioproliferative glomerulonephritis following a second admission with pneumococcal pneumonia . It is possible that the generation of the nephritic factor was initiated during the presenting illness.

Eur J Clin Invest, 1983 Apr, 13(2), 179 - 82
The normal occurrence of two molecular forms of the eight complement component (C8) and their concentrations in a family with C8 deficiency; Brandslund I et al.; A haemolytically inactive alpha-mobile complement C8 component was identified by crossed immunoelectrophoresis in a 27-year-old male with recurrent meningococcal infections and absence of complement mediated serum haemolytic activity . The patient's serum/plasma contained no demonstrable normal C8 . C8 inhibitor activity was not demonstrable in his serum and the alternative activation pathway appeared to be intact . Serum from the proband's parents and both siblings had normal total haemolytic complement activity and they were without symptoms . However, both the normal and the haemolytically inactive C8 protein were demonstrable in their sera . Their normal C8 concentrations were less than one-half of the normal C8 mean value and distinctly below the lowest value found in ten healthy persons . The concentration of the inactive C8 component in the proband's serum was roughly 1 . 5 times higher than that of the other family members, whereas its concentration in sera of the family members was between 1 . 8 and 2 . 5 times the highest concentration found in ten healthy donors, all of whom also had an alpha-mobile C8 in measurable quantities.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Apr, (4), 23 - 6
{Optimal inoculation doses of meningococcal chemical polyvalent ABC-vaccine for immunizing children of different ages . II . A study of the immunological effectiveness of different doses of the preparation}; Ganzenko VP et al.; The study of meningococcal chemical polyvalent ABC-vaccine, manufactured by the Mechnikov Research Institute for Vaccines and Sera (Moscow), was carried out with the aim of finding the optimum vaccination doses for the immunization of children aged 0.5-15 years . In this study the effectiveness of the vaccine was evaluated by the determination of the titers of specific bactericidal antibodies in paired serum samples obtained before and 30 days after immunization . The analysis of the frequency of positive seroconversions and the levels of the geometric mean antibody titers allowed the authors to reveal the presence of a distinct relationship between the intensity of antibody production and the dose of the vaccine under test, used for immunization, as well as to establish that pronounced immune response to the optimum dose developed in 95-100% of the vaccinees . Taking into account the results obtained in the earlier studies of the safety and reactogenicity of the preparation (see Communication I), the optimum vaccination doses for the immunization of children of different age groups were established . On the basis of the statistical analysis of the characteristics of immune response to different doses of the preparation the following doses were chosen as optimum: 80 micrograms for children aged 0.5-2 years, 100 micrograms for children aged 3-7 years, 120 micrograms for children aged 8-11 years, 160 micrograms for children aged 12-15 years.

Infect Immun, 1983 Apr, 40(1), 257 - 64
Importance of complement source in bactericidal activity of human antibody and murine monoclonal antibody to meningococcal group B polysaccharide; Zollinger WD et al.; The bactericidal activity of human antibody and murine monoclonal antibody to meningococcal group B polysaccharide was investigated as a function of the complement source . The immunoglobulin M murine monoclonal antibody 2-2-B was shown by several different methods to be highly specific for meningococcal group B and Escherichia coli K1 capsular polysaccharides . It had strong bactericidal activity in conjunction with either rabbit or human complement, but gave a higher titer with rabbit complement . A strong prozone was observed in each case . Human postvaccination antibody to meningococcal group B polysaccharide was strongly bactericidal with rabbit complement, but had little or no bactericidal activity in conjunction with human complement . Antibodies in adult normal human sera that were bactericidal with rabbit complement were also found to be predominantly directed against the meningococcal group B capsular polysaccharide . Human antibodies that were bactericidal with human complement appeared to be primarily directed against noncapsular antigens.

Ann Trop Med Parasitol, 1983 Apr, 77(2), 175 - 8
Failure of meningococcal vaccination to stop the transmission of meningococci in Nigerian schoolboys; Blakebrough IS et al.; A combined group A and group C meningococcal polysaccharide vaccine was given to 438 Nigerian schoolboys shortly before an outbreak of group A meningococcal disease occurred in their school . Four months after vaccination the carriage rate of group A meningococci among vaccinated subjects (11%) was no different from that found among the controls (12%), although a good antibody response to both components of the vaccine was observed . One case of group A meningococcal disease was recorded amongst 438 vaccinated subjects while five cases occurred among 874 controls.

Antibiotiki, 1983 Apr, 28(4), 271 - 8
{Effect of penicillin and the habitat medium in the body of bacterial carriers on the intercellular bonds in populations of the meningococcus and pertussis microbe}; Vysotskii VV et al.; The relationship of the bacterial cells in populations and their adhesion activity is at present one of the research priorities in microbiological studies . The stimulating effect of penicillin on the development of morphologically different intercellular bonds (IB) in populations of the pertussis causative agent and first of all derivatives or evaginates of the cell wall membranes was observed . Morphologically similar systems and polytubular IB were detected in populations of meningococcal strains isolated from carriers having no signs of the disease . Correlation between the after-effect of penicillin and the presence of the causative agent in bacterial carriers was shown . Unknown systems of interlacing tubular structures not directly bound with the cells, the walls of which were single contour membranes were determined in the meningococcal populations treated with penicillin . IB were observed in the population in the form of transpopulation cords . Morphologically different IB playing the role of specialized organelles might be considered as factors of the functional unity of the bacterial population as a multicellular system.

J Ultrastruct Res, 1983 Apr, 83(1), 21 - 7
Visualization of bacterial polysaccharides by scanning transmission electron microscopy; Wolanski BS et al.; Highly purified capsular polysaccharides of Neisseria meningitidis groups A, B, and C have been visualized by high resolution Scanning Transmission Electron Microscopy (STEM) . Spheroidal macromolecules approximately 200 A in diameter are characteristic of the Meningococcus A and C polysaccharides whereas filaments that are 400-600 A in length are found in Meningococcus B polysaccharide preparations . Filaments are occasionally found associated with the spheroidal Meningococcus A and C polysaccharides and it is proposed that these structures are composed of a long (1-4 microns) filament or filaments that are arranged in spheroidal molecules or micelles of high molecular weight . The Meningococcus B polysaccharide, by contrast, is a short flexuous filament or strand of relatively low molecular weight . A relationship between morphology and antigenicity is proposed.

Infect Immun, 1983 Apr, 40(1), 39 - 45
Preparation and immunochemical characterization of meningococcal group C polysaccharide-tetanus toxoid conjugates as a new generation of vaccines; Beuvery EC et al.; Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugates have been prepared by using high-molecular-weight polysaccharide and purified tetanus toxoid and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide as a coupling reagent . The influence of three conditions of preparation was studied . Biochemical assays, the enzyme-linked immunosorbent assay, and isopycnic CsCl gradient ultracentrifugation have been used to characterize the conjugates . The polysaccharide-to-protein ratios of the various conjugate preparations showed differences . The ability of the group C polysaccharide component to react with specific antibodies was reduced, whereas most of the tetanus toxoid seemed to be hidden by the polysaccharide . The composition of the conjugate was not homogeneous, and at least 10% of free polysaccharide was present . Thermostability in lyophilized condition in the presence of lactose was excellent.

Infect Immun, 1983 Apr, 40(1), 398 - 406
Immunogenicity of meningococcal antigens as detected in patient sera; Poolman JT et al.; The immunogenicity of meningococcal surface antigens was tested in acute- and convalescent-phase sera from patients with meningococcal diseases by enzyme-linked immunosorbent assay and gel immunoradioassay . In gel immunoradioassay, the antigens are separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis before testing their antibody-binding capacity . Both 125I-labeled protein A and 125I-labeled anti-human immunoglobulin G were used to detect antibody binding . It appeared that the variable, low-molecular-weight, heat-modifiable major outer membrane proteins (molecular weights, 25,000 to 32,000) induced strong, strain-specific immunoglobulin G antibody responses . In addition, pili induced strong, cross-reactive antibody responses that could be detected with 125I-labeled protein A, but not with 125I-labeled anti-immunoglobulin G . Antibody responses against capsular polysaccharides, lipopolysaccharides, and minor outer membrane proteins could also be detected by gel immunoradioassay . When tested by enzyme-linked immunosorbent assay against outer membrane complexes, patient sera demonstrated a large amount of cross-reactivity against heterologous meningococcal strains.

S Afr Med J, 1983 Mar 26, 63(13), 498 - 500
Early clinical diagnosis of the syndrome of inappropriate secretion of antidiuretic hormone . Case reports; Househam KC et al.; Two children with inappropriate antidiuretic hormone secretion associated with meningococcal septicaemia are described . The syndrome was diagnosed despite the patients' serum sodium concentrations being within the normal range when, with normal fluid intake and in the absence of hypovolaemia, they developed oliguria and concentrated urine . Early diagnosis prevents cerebral water intoxication and pulmonary oedema that may occur if hyponatraemia is allowed to develop.

An Esp Pediatr, 1983 Mar, 18(3), 224 - 31
{Hypophosphoremia and meningococcal infection . Preliminary study}; Labay Matias MV et al.; Serum phosphorus showing anomaly low values: 2.47 +/- 0.41 mg/dl (p less than 0.001) were determined within the first hours of admittance in 18 children with meningococcal infection . In another 10 renal clearance was performed founding phosphatemias of 2.35 +/- 0.37 mg/dl (p less than 0.002), determining FE of electrolytes . Both groups were compared with another one without infectious pathology which presented normal phosphatemia . Most serious cases had the most severe hypophosphatemia (p less than 0.01); eight children presented hyperphosphaturia up to 52.7 mg/Kg/day and TRP lower than 80%; six asymptomatic hypocalcemia, two hypomagnesemia; FE of potassium was elevated in three children, FE of calcium in one child and FE phosphorus in eight children . Monosodium phosphate was administered to two children with myocarditis as they presented signs of hypophosphatemia . All of them normalized biochemically in 3-4 days . Possible physiopathological mechanisms of this situation are discussed, considering the possibility that hormonal and/or tubular mechanisms take part in the lowering of phosphorus . Necessity of monitoring serum and urine phosphorus in these children is emphasized.

J Infect, 1983 Mar, 6(2), 147 - 56
Longitudinal study of asymptomatic meningococcal carriage in two Belgian populations of schoolchildren; De Wals P et al.; In Brussels, a 15-month longitudinal survey was conducted in two primary schools, from March 1975 to May 1976, in order to analyse the dynamic of asymptomatic meningococcal carriage, during an epidemic mainly caused by serogroup B, serotype 2 Neisseria meningitidis . In the first school, which is situated in a suburban area with upper-middle socio-economic status of residents, a mean prevalence of carriers of 10 per cent, an acquisition rate of eight per 1000 months, and a mean duration of carriage of 12.4 months were observed among 158 schoolchildren aged six to 11 years old . In the second school, which is situated in a densely populated area with low socio-economic status of residents, a mean prevalence of carriers of 33 per cent, an acquisition rate of 28 per 1000 months, and a mean duration of carriage of 11.7 months were observed among 203 schoolchildren aged three to 14 years old . For both schools, the median duration of carriage was estimated at 9.4 months . The differences of prevalence and incidence of acquisition between the two schools cannot be explained by age, sex or ethnic factors and are probably related to socio familial variables . The theoretical relationship between prevalence, incidence and duration of meningococcal carriage was for the first time demonstrated in this study . The results also suggest that populations of low socio-economic status and living in densely populated areas constitute a target population for meningococcal disease prevention.

Am J Med, 1983 Mar, 74(3), 361 - 8
Reversible "end-stage" lupus nephritis . Analysis of patients able to discontinue dialysis; Kimberly RP et al.; Seventeen of 41 patients with lupus nephritis who underwent dialysis for renal failure recovered renal function and discontinued dialysis . Two of these 17 had confounding factors unrelated to lupus that contributed to renal dysfunction (one meningococcemia, one vigorous diuresis) . Indications for dialysis were identical both in patients who discontinued dialysis (short-term) and in those who did not (long-term) . The rate of progression to dialysis, measured as the slope of the reciprocal of the serum creatinine level versus time, was significantly more rapid in the short-term group (p less than 0.001) . Patients who underwent short-term dialysis were more likely to have had lupus for less than two years (p = 0.015) . Anti-DNA antibody binding values, total hemolytic complement levels, extent of extrarenal disease, and hypertension did not differentiate the short-term from long-term dialysis groups . Renal biopsy performed within three months of first dialysis did not demonstrate a consistent picture in the short-term dialysis group . Dialysis is not equivalent to irrevocable end-stage renal disease in patients with lupus nephritis . Thirteen of 22 patients (59 percent) with a 10 percent reduction time for renal function of less than three weeks were able to discontinue dialysis . Ten of these 13 were alive without need for dialysis six months later, with a mean follow-up serum creatinine level of 2.9 +/- 1.9 mg/dl.

Am J Dis Child, 1983 Mar, 137(3), 279 - 81
Skeletal lesions following meningococcemia and disseminated intravascular coagulation . A recognizable skeletal dystrophy; Robinow M et al.; Partial destruction of the right humeral and right femoral head were discovered in a 30-month-old girl, two years after her recovery from meningococcal septicemia and disseminated intravascular coagulation (DIC) . Additional findings were symmetrical epiphyseal-metaphyseal lesions of the lower femora and upper and lower tibiae . The combined skeletal lesions seem to be characteristic sequelae of infantile meningococcemia complicated by DIC . Since this condition is no longer uniformly fatal, the characteristic skeletal dystrophy will be encountered more frequently and should be recognized by radiologists, pediatricians, and orthopedists . The features shared by our patient and the seven previously published cases are presented.

Eur J Immunol, 1983 Mar, 13(3), 262 - 4
Immunoglobulin isotype in the murine response to polysaccharide antigens; Moreno C et al.; Murine antisera specific for the alpha (1 leads to 3) and alpha (1 leads to 6)-linked glucosyl determinants of dextran, as well as for meningococcal polysaccharide group C, have been examined for the distribution of their immunoglobulin classes and subclasses . Whereas the thymus-independent anti-alpha (1 leads to 3) dextran response in BALB/c mice was found to be IgM greater than IgG3 greater than IgA, thus corresponding to previously published work, neither the alpha (1 leads to 6) response in its thymus-dependent or-independent form, nor the response to purified meningococcal polysaccharide, corresponded to this pattern . No preference for any of the IgG subclasses appeared for these antigens when given as thymus-independent carbohydrates . On the other hand, thymus-dependent forms of alpha (1 leads to 6) dextran showed an IgG1 greater than IgG3 greater than IgG2 pattern.

Bull Eur Physiopathol Respir, 1983 Mar-Apr, 19(2), 81 - 7
{Bacterial surface and phagocytosis}; Orfila J; Phagocytosis is a host's front line of cellular defence against bacteria . Some anatomical structures of the bacterial envelope may hinder this cellular activity . Amongst the most important constituents of the cell envelope, the capsule plays a very important role, its biochemical components being polysaccharide (pneumococcus, meningococcus), M proteins (streptococcus, yersinia, E . coli), mucopeptide (staphylococcus) or hyaluronic acid (streptococcus, Treponema pallidum) . Complement plays an outstanding role by increasing the phagocytosis index . The studies of the different factors of the complement show that the degree of phagocytosis is correlated with the amount of C3 fixed on the surface of the bacteria . We still do not know the exact nature of the cell receptors, but the surface properties of the host cell and of the bacteria determine the contact angle which is of importance in this process.

Can J Microbiol, 1983 Mar, 29(3), 369 - 76
Effect of subinhibitory concentrations of antimicrobials on meningococcal adherence; Salit IE; Meningococci adhere to human pharyngeal cells and agglutinate erythrocytes . These events are dependent upon pili and are reduced by encapsulation . The effect of subinhibitory concentrations of seven antimicrobials on meningococcal adherence, antimicrobials on meningococcal adherence, piliation, hemagglutination (HA), and bacterial proteins was studied to determine their potential for modifying virulence . Piliation was reduced by most antibiotics but was most markedly (greater than 70%) reduced by rifampin, tobramycin, and VCN (vancomycin, colistin, and nystatin) . Bacterial proteins as determined by sodium dodecyl sulphate--polyacrylamide gel electrophoresis were altered: tetracycline, sulfamethoxazole, rifampin, and VCN caused loss of a 43-45 K protein and a general decrease in all stainable protein bands, while erythromycin, ampicillin, and tobramycin only caused an increase in a 28 K protein . HA was reduced by ampicillin, tobramycin, erythromycin, and VCN but interstrain variability was present . Epithelial cell adherence was diminished by an average of 45% compared to controls . The meningococcal strains lost HA, piliation, and adherence in the same rank order, however, there was no significant rank correlation of antibiotic inhibitory activities on these parameters . These results indicate that subinhibitory antibiotic concentrations reduce meningococcal piliation and alter other bacterial proteins; these changes are associated with diminished adherence and hemagglutination, alterations which may be markers of meningococcal virulence.

Thromb Haemost, 1983 Feb 28, 49(1), 5 - 7
Increased tissue thromboplastin activity in monocytes of patients with meningococcal infection: related to an unfavourable prognosis; Osterud B et al.; In 16 patients, 13 with meningococcal infection and 3 suspected to have this infection, 8 patients were found to possess significant higher level of tissue thromboplastin activity of their monocytes isolated from the blood at the admission to the hospital than normal . Five of those 8 patients had an extremely high concentration, greater than 60-300 fold increase, and all these patients died . The exposed tissue thromboplastin activity on the surface of the endotoxin stimulated monocytes is probably the direct inducer of disseminated intravascular coagulation (DIC) in meningococcal infection.

Carbohydr Res, 1983 Feb 16, 113(1), 57 - 62
omega-Aminoalkyl beta-glycosides of N-acetylmuramyl-L-alanyl-D-isoglutamine, and their conjugates with meningococcal group C polysaccharide; Ponpipom MM et al.; The 6-aminohexyl beta-glycoside of N-acetylmuramyl-L-alanyl-D-isoglutamine and its spacer-arm-linked analog (3.8 nm) were synthesized from 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-alpha-D-glucopyrano)-{2,1-d}-2- oxazoline, and coupled with meningococcal group C polysaccharide in attempts to enhance the immunogenicity of the polysaccharide antigen.

Carbohydr Res, 1983 Feb 16, 113(1), 45 - 56
Methyl beta-glycosides of N-acetyl-6-O-(omega-aminoacyl)muramyl-L-alanyl-D-isoglutamines, and their conjugates with meningococcal group C polysaccharide; Ponpipom MM et al.; Spacer arms 2.1-3.7 nm (21-37 A) long were prepared, and coupled with the methyl beta-glycoside of N-acetylmuramyl-L-alanyl-D-isoglutamine benzyl ester, to give blocked 6-acylates . Deprotection was effected with palladium chloride and triethyl-silane . Chemical conjugates of MDP-meningococcal group C polysaccharide were then synthesized, in attempts to enhance the immunogenicity of the polysaccharide antigen.

J Gen Microbiol, 1983 Feb, 129 (Pt 2), 447 - 52
Immunological relationship between the capsular polysaccharides of Neisseria meningitidis serogroups Z and 29E; Griffiss JM et al.; The immunological relationship between serogroups 29E and Z of Neisseria meningitidis was investigated using bacterial agglutination, precipitin-in-gel, primary antigen binding and immune lysis assays . The two capsular polysaccharides were both cross immunogenic and cross reactive . Demonstration of the relationship using group Z antisera depended on which assay was used . It was most readily apparent in assays of immune lysis, less apparent when precipitins were sought in gel and inapparent when bacterial agglutination, the standard assay for determining serogroup, was employed . The cross reacting epitope was expressed 10-fold more within the group 29E polysaccharide than within the group Z polysaccharide . These findings imply that inclusion of either polysaccharide in a polyvalent meningococcal vaccine may obviate the need to include the other polysaccharide.

Zh Mikrobiol Epidemiol Immunobiol, 1983 Feb, (2), 70 - 3
{Diagnostic test-system for the immunoenzymatic detection of meningococcal antigen}; Shabalina SV et al.; To detect meningococcal antigen, the use of the enzyme-labeled immunosorbent assay (ELISA), a new variant of the immunoenzymatic method, permitting one to carry out quantitative analysis, is proposed . The optimum conditions for the test to detect group A meningococcal antigen, as well as the procedure for the approbation of the test on patients with meningococcal infection and on healthy persons, have been worked out . The method is shown to be highly specific and sensitive.

J Infect Dis, 1983 Feb, 147(2), 282 - 92
Association of virulence of Neisseria meningitidis with transparent colony type and low-molecular-weight outer membrane proteins; Stephens DS et al.; To assess the factors that might be associated with the virulence of Neisseria meningitidis, isolates from the blood or cerebrospinal fluid of patients with meningococcal disease and meningococcal isolates from the nasopharynx of asymptomatic carriers were compared with regard to opacity or transparency of colonies . Neisseria meningitidis isolated from patients with meningitis and septicemia grew in predominantly transparent colonies, whereas meningococci isolated from asymptomatic carriers generally formed opaque or a mixture of opaque and transparent colonies . Piliated meningococci from opaque colonies attached to human mucosal cells in significantly greater numbers than did piliated meningococci from transparent colonies of the same isolate . Meningococci from transparent colonies were more resistant to killing by normal human serum than were meningococci from isogenic opaque colonies . Disease-associated isolates that formed transparent colonies contained one or more heat-modifiable outer membrane proteins of molecular weight 26,000-32,000 which were not found in some isogenic clones that formed opaque colonies . Transparency of meningococcal colonies may be an important marker for factors that mediate meningococcal virulence.

J Hyg (Lond), 1983 Feb, 90(1), 49 - 54
Meningococcal disease in South Australia: incidence and serogroup distribution 1971-1980; Hansman D; During the ten-year period 1971-80 isolates of meningococci from 85 cases of meningococcal disease (MD) in South Australia, from 66 children, 6 adolescents and 13 adults, were examined . These comprised 69 cases of meningitis and 16 cases of bacteraemia without meningitis . Thirty-three (39%) of all cases of MD occurred in children less than 1 year of age, the median age was 19 months . Serogroup B accounted for 61 (72%) cases of MD, group A seven (8%), group C seven (8%), group W135 five (6%), group Y three (4%) and group X one (1%); in addition there was a single case of Neisseria lactamica infection . The annual prevalence of MD in South Australia for the period was 11 cases per 100000 for children under the age of 2 years and 0.7 cases per 100000 overall . The prevalence was highest in winter (45% cases) and spring (26%) and lowest in summer (13%) . The overall mortality rate was 8% . Four of the 21 infants under the age of 6 months died (mortality rate 19%) whereas none of the 32 children aged from 6 months to 14 years died (P = 0.02) . Amongst the survivors, three children had deafness, which was bilateral and severe in two.

J Infect Dis, 1983 Feb, 147(2), 247 - 51
Differentiation of neisseriaceae by isoenzyme electrophoresis; Braude AI et al.; Analysis of 71 strains of Neisseriaceae by starch-gel electrophoresis of hexokinase, phosphoglucomutase, glucose phosphate isomerase, and L-malate-nicotinamide adenine dinucleotide phosphate oxidoreductase showed that all gonococci and all memingococci have a characteristic hexokinase isoenzyme that is specific for each species and clearly distinguishes meningococci and gonococci from each other and from other species of Neisseriaceae . Strains of gonococci that were transformed into maltose utilizers by DNA from Neisseria lactamica and Neisseria meningitidis showed no change in the isoenzymes so that they could still be differentiated from meningococci and other Neisseriaceae by isoenzyme electrophoresis . In view of the limited sensitivity and specificity of conventional tests for the identification of gonococci and the possibility that gonococci may be transformed into maltose utilizers by DNA from normal throat flora, electrophoresis of hexokinase isoenzymes should be useful for the precise laboratory identification of the pathogenic neisseriae, especially those from atypical sites and those giving indeterminate reactions.

Carbohydr Res, 1983 Jan 16, 112(1), 105 - 11
The structure of the capsular polysaccharide obtained from a new serogroup (L) of Neisseria meningitidis; Jennings HJ et al.; A newly isolated serogroup of Neisseria meningitidis (serogroup L), obtained from contacts of a patient with meningococcal meningitis, elaborates a structurally unique, capsular polysaccharide . The polysaccharide contains only 2-acetamido-2-deoxy-D-glucosyl and phosphate constituents in the molar ratio of 3:1, and is composed of the following repeating unit.

Neurol Neurochir Pol, 1983 Jan-Feb, 17(1), 25 - 31
{Fluorescence method of evaluation of the lysosomes of the lymphoid cells of the cerebrospinal fluid in meningitis and meningism}; Kucharska-Demczuk K; The fluorescence method of Blume et al . was found to be useful for identification and morphological evaluation of lysosomes in cerebrospinal fluid cells . The investigations were carried out in 49 patients with viral and bacterial meningitis or meningismus . It was demonstrated that the CSF cells in most patients with purulent meningitis contained no fluorescent granules in an early stage of the disease before introduction of antibacterial therapy . These granules were found in CSF cells in cases of leptospirosis, viral meningitis and meningismus of various aetiology in acute stage of the disease and even in convalescence, and in purulent meningitis in convalescence . In bacterial meningitis large lysosomal granules were observed, and in viral meningitis these granules were small . The method visualizes easily bacteria (meningococci and pneumococci) in the cerebrospinal fluid.

An Esp Pediatr, 1983 Jan, 18(1), 5 - 9
{Pharmacologic evaluation of penicillin in children with meningococcal meningitis}; Ribes C et al.; Levels of penicillin both in blood and CSF are determined in 11 children with meningococcal meningitis . Authors compare these values with MIC . The therapeutic pattern was 500.000 Ul/Kg/day of benzylpenicillin, in six doses, with a single initial doses of 200.000 Ul/Kg . The results recommend not to use a lower doses in order to assure a permanently efficient penicillin concentration.

Ann Acad Med Singapore, 1983 Jan, 12(1), 98 - 102
Bacterial infections of the skin . II: cutaneous clues to systemic infections; Chan HL; Systemic bacterial infections often produce skin signs which are of help in the elucidation and evaluation of these diseases . This paper reviews some of such cutaneous clues, their occurrence, recognition and value . The following conditions are discussed: bacterial endocarditis, pseudomonas septicaemia, disseminated gonococcal infection, meningococcemia, clostridia infections, leptospirosis and typhoid fever . Bacterial causes of erythema nodosum are also considered.

J Biol Stand, 1983 Jan, 11(1), 65 - 74
Immunoelectrophoretic characterization of the molecular weight polydispersion of polysaccharides in multivalent bacterial capsular polysaccharide vaccines; Porro M et al.; The molecular weight polydispersion of single antigens present in multivalent bacterial capsular polysaccharide vaccines has been characterized by an immunoelectrophoretic method . Chromatographic effluents from Sepharose gel of bacterial capsular polysaccharide vaccines were tested by fused-rocket immunoelectrophoresis and the distribution coefficient (Kd) of each polysaccharide present in the mixture was calculated . The method appeared to be efficient and reproducible . However, different Kd values were obtained by immunoelectrophoretic and chemical or physical analysis of the chromatographic effluents of each single polysaccharide component . The use of this immunoelectrophoretic procedure was extended to the potency control of multivalent meningococcal and pneumococcal polysaccharide vaccines in order to detect changes in the molecular weight polydispersion of each antigen with time.

J Clin Microbiol, 1983 Jan, 17(1), 85 - 91
Characteristics of pathogenic Neisseria spp . isolated from homosexual men; Janda WM et al.; Oropharyngeal, urethral, and rectal cultures for pathogenic Neisseria spp . were collected from 815 homosexual men attending a community clinic in Chicago . Meningococci were characterized by serogrouping and antimicrobial susceptibility testing . Gonococci were auxotyped, and susceptibilities to penicillin and tetracycline were determined . Of the 815 men tested, 42.5% carried meningococci in the oropharynx . Gonococci were recovered from the urethra, rectum, and oropharynx of 18.5, 16.3, and 5.6%, respectively . Meningococci were also recovered from the urethra (6 patients) and the rectum (15 patients) . Some of these isolates were identical to the isolates from the oropharynges of the same patients, whereas others were distinct from the oropharyngeal isolates by serogroup or antimicrobial susceptibilities . Serogroups B, W135, and C comprised over 90% of the meningococci . Almost 80% of the gonococcal strains required minimal inhibitory concentrations greater than 0.06 micrograms of penicillin per ml, whereas greater than 90% of the meningococci were inhibited at this concentration . Auxotyping demonstrated three major auxotypes: Zero (required none of the nutrients tested), 60%; arginine requiring, 19.4%; and proline requiring, 12.3% . Only four strains (1.2%) required arginine, hypoxanthine, and uracil.

Infect Immun, 1983 Jan, 39(1), 50 - 9
Turnover in the transferrin iron pool during the hypoferremic phase of experimental Neisseria meningitidis infection in mice; Letendre ED et al.; Mouse transferrin was used to specifically label the plasma transferrin iron pool for studies of iron kinetics in normal mice and infected mice during the hypoferremic phase of experimental meningococcal infection . The plasma transferrin iron pool of normal mice was found to be very dynamic, with a half-life of iron in the pool of 0.7 h . Iron left the plasma pool, entered the bone marrow, and was released into the blood in erythrocytes . Iron from the transferrin pool also entered the liver and spleen and was presumably in the reticuloendothelial system components of these organs . Most of the iron that had been supplied as transferrin iron was found in erythrocytes by 48 h after injection . Studies with mice infected with Neisseria meningitidis strain M1011 revealed similar kinetics for transferrin iron . There was no redistribution of iron within the various iron pools as a result of infection . Iron turnover in the plasma transferrin pool during the hypoferremic phase was similar to control rates, and iron leaving the pool entered its normal erythroid compartments . The lack of accelerated turnover of plasma iron and the finding that plasma iron was not rerouted to storage compartments during the hypoferremic phase provided good evidence that lactoferrin and leukocytic endogenous mediator were not directly involved in redirecting transferrin iron . Our evidence has implicated an impaired return of reticuloendothelial system-processed iron to the transferrin pool during the hypoferremic response . This appears to be a logical point in the erythroid iron cycle for host-mediated iron sequestration, as the reticuloendothelial system is involved in iron storage and may regulate iron levels in the plasma transferrin pool under normal conditions.

Scand J Infect Dis, 1983, 15(4), 339 - 45
Fulminant meningococcal infections in a family with inherited deficiency of properdin; Braconier JH et al.; Three males in a large kindred died of meningococcal infections . In the index patient, properdin (P) was not detectable in serum . Two healthy males with a selective P deficiency were found in the family . There was no general susceptibility to infections, nor to other diseases as suggested by the family history . The serum bactericidal activity for Neisseria meningitidis group C, isolated from the index patient, was moderately reduced in P deficient serum, and was improved by addition of purified P.

Rev Epidemiol Sante Publique, 1983, 31(3), 273 - 82
{Policy for the prevention of meningococcal infections in Belgium}; De Wals P; An outbreak of meningococcal disease occurred in Belgium from 1969 to 1975 . It was caused by serogroup B, serotype 2 organisms . As there is no effective vaccine against serogroup B meningococci, the aim of prophylaxis is to prevent the occurrence of secondary cases among contacts of patients . Epidemiologic studies were carried out during the outbreak . A significant risk of secondary case was shown to be associated with household, day-care nursery, and pre-elementary school exposure . In most instances, the prophylactic measures prescribed by physicians were inappropriate . The effectiveness of prevention was low . A new prophylactic policy was defined, combining the identification of high risk contacts, the close medical supervision of these contacts ant the prescription of effective chemoprophylactic drugs . The Belgian experience illustrates some of the problems and difficulties associated with the use of the results of epidemiologic studies for health policy making.

Cancer Immunol Immunother, 1983, 15(3), 217 - 20
Menningococcal antigens (MA): a novel immune stimulant in experimental neoplasia; Teodorczyk-Injeyan JA et al.; An extract of the meningococcus antigens (MA) prepared from N . meningitidis was tested for an anti-tumor effect in rat and murine metastasizing tumor models . Effectiveness of MA in each model varied with dose and was manifested as significantly improved survival of the treated animals . Growth of the primary Fischer bladder carcinoma (FBCa) and metastases to lungs and lymph nodes were significantly inhibited in F344 rats treated weekly with 1 mg MA . Administration of MA at 100 micrograms per animal significantly prolonged survival of P815 mastocytoma-inoculated DBA/2 mice . Survival of C-26 colon adenocarcinoma-bearing Balb/c mice was significantly improved in animals that received weekly injections of 20 micrograms MA, without significant effect on the development of local tumor . The meningococcal antigens demonstrate strong mitogenic activity in B-cell-enriched murine spleen cultures . Thus the immunostimulatory activity of MA in experimental malignancy could involve, directly or indirectly, activation of B lymphocytes.

J Infect, 1983 Jan, 6(1), 55 - 60
Recurrent meningococcal meningitis due to partial complement defects and poor anti-meningococcal antibody response; Herva E et al.; An otherwise healthy young man had three episodes of meningococcal meningitis within three years . The last episode was caused by group A, and occurred four weeks after the patient received group A vaccine, thus representing one of the very few failures of this vaccine . The specific susceptibility to meningococcal infections was connected with half-normal levels of several components of the complement system (C3, C4, C9, factor B, properdin), and reduced antibody responses to group A and group C meningococcal polysaccharides, but not to several other polysaccharide or protein antigens.

J Infect, 1983 Jan, 6(1), 49 - 54
Ano-genital gonorrhoea and pharyngeal colonisation with meningococci: a serogroup analysis; Young H et al.; Among patients attending a clinic for sexually transmitted diseases, women without gonorrhoea were significantly less likely to be colonised with meningococci than were women with gonorrhoea, men with gonorrhoea and men without gonorrhoea: the respective carriage rates (per cent) for groupable plus non-groupable meningococci were 16, 26, 23 and 31 . Considering groupable and non-groupable meningococci separately it was found that women without gonorrhoea were also significantly less likely to be colonised with groupable meningococci but there were no significant differences in the carriage rates of non-groupable meningococci . The association between ano-genital gonorrhoea and meningococcal colonisation of the pharynx observed previously with certain groups of patients most likely results from increased mouth-to-mouth contact in 'high-risk' patients rather than individual susceptibility to neisserial infection . The possibility that there is a difference in the predominant means of spread of groupable and non-groupable meningococci is discussed.

Padiatr Padol, 1983, 18(1), 11 - 20
{Bactericidal action of chloramphenicol and synergism with beta-lactam antibiotics}; Guggenbichler JP; Excellent clinical results were observed with the combination therapy of chloramphenicol with beta-lactam-antibiotics in the treatment of purulent meningitis . This came as a surprise as bacteriostatic antibiotics like chloramphenicol are commonly thought to antagonize the bactericidal action of penicillin or ampicillin . We reevaluated the mode of action of chloramphenicol against the three most common meningeal pathogens after the newborn period . Chloramphenicol was found to be bactericidal against H . influenzae, Streptococcus pneumoniae and Neisseria meningitidis at clinically achievable levels in the CSF . In addition chloramphenicol showed synergistic action with ampicillin against H . influenzae which can possess clinical relevance particularly with the high inoculum of 10(7) organisms/ml which is frequently seen in bacterial meningitis . No synergism was found against Pneumococci and Meningococci but also no antagonism of the lower MIC and MBC values seen with ampicillin and penicillin G . The combination of chloramphenicol with either penicillin or ampicillin constitutes a clinically successful therapeutic regimen which is now also proven by in vitro investigations.

J Biol Stand, 1983 Jan, 11(1), 55 - 64
The quantitative immunochemical determination of pneumococcal and meningococcal capsular polysaccharides by light scattering rate nephelometry; Lee CJ; A quantitative nephelometric method was used for the measurement of the individual pneumococcal, as well as meningococcal, polysaccharides in the polyvalent vaccine final containers . This method is simple, rapid, inexpensive, and provides both qualitative and quantitative analyses of the polyvalent polysaccharide vaccines . By this method the individual pneumococcal types, 1, 2, 3, 4, 6A, 7F, 8, 9N, 12F, 14, 18C, 19F, 23F and 25 polysaccharides, were found to be present at 90-114% of the manufacturer's indicated concentrations; meningococcal group A, C, Y and W135 polysaccharides were at 90-108% of the manufacturer's listed concentrations . This nephelometric method coupled with gel filtration can also be used for measurement of the molecular sizes or stability of individual polysaccharides in the final container . Pneumococcal polysaccharide types 3, 6A, 9N and 19F, used as representative types, were treated with 0.5 N hydrochloric acid . The molecular sizes for types 3 and 9 N polysaccharides were stable to acid treatment . In contrast, types 6A and 19F polysaccharides were degraded . Heating meningococcal groups A, C, Y and W135 polysaccharides at 37 degrees C for 48 h did not affect their molecular size in the polyvalent vaccine.

Can J Microbiol, 1983 Jan, 29(1), 129 - 36
Serotypes of Neisseria meningitidis associated with an increased incidence of meningitis cases in the Hamilton area, Ontario, during 1978 and 1979; Ashton FE et al.; The distribution of serotypes among strains of Neisseria meningitidis responsible for a marked increase of meningitis cases in the Hamilton area, Ontario, in 1978 and 1979 was determined . Twenty-six serogroup B and two serogroup W135 strains isolated from cerebrospinal fluid, blood, and skin of 28 patients were serotyped by agar gel double diffusion . Twenty-one (81%) of the group B strains were serotype 2b as judged by the formation of characteristic serotype precipitin bands with the specific anti-2996 (type 2b) serum . Fourteen of the serotype 2b strains also reacted with anti-77252 serum, which suggested that one strain or several closely related strains were mainly responsible for the increase in meningitis during the 2-year period . Examination of the outer membrane complexes (OMC) of the strains by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) revealed that all 21 of the serotype 2b strains contained the class 2 protein (molecular weight 41500) which is known to be the site of the serotype 2b determinant . Further characterization of the serotype 2b, 77252 strains by enzyme-linked immunosorbent assays (ELISA) and SDS-PAGE suggested that the 77252 determinant was present in the class 1 proteins of these strains . The serotype 2b containing strains were isolated from 77.7 and 70% of males and females, respectively, from 81.8% of children less than 5 years of age, and from 75.0% of patients of all age groups . The study indicates the important role of serotype 2b meningococci in causing the increased incidence of meningitis and further substantiates the important association of the serotype 2b determinant with group B serotype 2 meningococcal disease in Canada.

J Infect Dis, 1983 Jan, 147(1), 68 - 76
Evaluation of immunotherapeutic approaches for the potential treatment of infections caused by K1-positive Escherichia coli; Cross AS et al.; Levels of antibody to the K1 polysaccharide capsule were examined in sera from patients naturally infected with K1-positive Escherichia coli, in sera from volunteers vaccinated with a group B meningococcal vaccine, in immune globulin prepared for intravenous use, and in a preparation of murine IgM monoclonal antibody to group B meningococci . In a phagocytic assay, the monoclonal antibody in mouse ascites fluid killed K1-positive E . coli to a final dilution of 1:250,000 (48 ng of antibody protein/ml); no killing was observed with any of the other antibody sources . This monoclonal antibody, which required human complement and exhibited a prozone when high concentrations of antibody (greater than 6 micrograms/ml) were used, killed all K1-positive strains but none of the K1-negative strains of E . coli tested . Levels of K1-binding antibody in the sera of vaccinated volunteers exceeded antibody levels resulting from natural infection or present in commercially prepared immunoglobulin and were less than those obtained in mouse ascites fluid containing the monoclonal antibody.

Infect Immun, 1983 Jan, 39(1), 247 - 52
Safety and immunogenicity of a group 29E meningococcal capsular polysaccharide vaccine in adults; Griffiss JM et al.; A serogroup 29E Neisseria meningitidis capsular polysaccharide vaccine at a dose of 50 micrograms was injected subcutaneously into 10 adult human volunteers . One vaccinate experienced a mild systemic reaction; one complained of moderate to severe local pain and tenderness . The vaccine induced significant homologous binding and bactericidal antibody by 2 weeks and significant binding antibody against the heterologous serogroup Z capsular polysaccharide by 4 weeks . Although binding antibody rose during the first 4 weeks and then declined slowly over the subsequent 4 months, bactericidal antibody response declined substantially by 4 and 8 weeks for both polysaccharides . The increase in group 29E bactericidal activity was no longer significant at 4 and 8 weeks; loss of bactericidal activity against group Z was significant by 8 weeks . Bactericidal activity again rose between 8 and 26 weeks, becoming significantly increased over prevaccination levels for group 29E and increased, though not significantly (P = 0.085), over prevaccination levels for group Z . As a result of the failure of induced antibody to increase bactericidal activity, only 40% of vaccinates achieved a greater than 2 log2 increase in lytic activity against group 29E, and none achieved this large an increase in lytic activity against group Z.

Rev Infect Dis, 1983 Jan-Feb, 5(1), 71 - 91
Meningococcal disease: still with us; Peltola H; In spite of considerable success in the development of drugs and vaccines, the problem of disease due to Neisseria meningitidis is far from solved . As late as the 1970s, epidemics of meningococcal disease occurred in at least 30 countries in all parts of the world . Most of the epidemics were caused by group A organisms, but epidemics due to groups B and C also took place occasionally . The case/fatality rate was usually less than 10% among patients with true meningitis; among those with "pure" septicemia, it was as high as 70% . Children less than five years old are most prone to meningococcal disease, but mortality is often highest among young adults . Because close contacts of the index case are at considerable risk--at least several hundred times higher than in the rest of the population--they should be protected immediately with an appropriate antibiotic and, if possible, with a vaccine as well . At the present time, however, no vaccine is available for use against group B organisms, which in nonepidemic conditions are the most prevalent of all meningococci.

Arkh Patol, 1983, 45(5), 43 - 8
{Chronic isolated brain lesions caused by respiratory viruses in children}; Tsinzerling VA et al.; Combined study of 48 postmortem observations of cerebral lesions caused mainly by meningococcal infection in children was carried out . In 15 cases, isolated subclinical involvement of the brain (more frequently, of the vascular plexus and meninges) caused by influenza A viruses (8 cases), B (2 cases), adenoviruses (6), parainfluenza and respiratory syncytial virus (1 each), and chlamydia (2) was found . This was proved by the presence of the appropriate antigens in the brain revealed by immunofluorescence which were absent in respiratory organs, high titres of antibody to the same agents in the cerebrospinal fluid which were lacking in 13 cases or had significantly low titres in 2 cases in the blood, virus isolation from the brain (2 cases) and detection of virus particles in 1 out of 2 cases from which the vascular plexus was examined by electron microscopy . Histological examination of the affected areas revealed structural changes of ependymocytes which were principally similar to those described in respiratory organs as well as in other organs in cases of generalization of respiratory infections . Different degrees of sclerosis of vascular plexus (2 cases) or meninges (2 cases) were also observed.

Cor Vasa, 1983, 25(6), 443 - 9
Vascular changes in hyperacute meningococcal sepsis as a manifestation of pathogenic action of immune complexes; Gurevich PS et al.; The analysis of post mortem examinations of 175 cases of meningococcal sepsis concentrates on a description of vascular changes as the chief manifestation of the given disease . The changes consisted in the destruction of the endothelium, mucoid swelling or fibrinoid changes of the wall of minute vessels, and disseminated intravascular blood clotting . In sum, these changes can be described as generalized microangiothrombopathy . In the affected vascular walls and in the thrombotic masses the presence of antigen-antibody immune complexes was found . It is therefore possible to regard hyperacute meningococcal sepsis as a manifestation of pathogenic action of immune complexes--as a consequence of massive blood invasion by antigen and of rapid formation of a great number of antigen-antibody complexes.

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