Rev Neurol (Paris), 1992, 148(3), 237 - 8 {Recurrent Neisseria meningitidis meningitis associated with homozygote complement C7 fraction deficiency}; Angibaud G et al.; A 20-year old man had three episodes of meningococcal meningitis . Complement assays showed a complete deficiency of the seventh component of the complement system . This case emphasizes the need to perform complement assays in young patients with recurrent bacterial meningitis. Bull Pan Am Health Organ, 1992, 26(1), 95 - 6 New children's vaccine initiative launched; ELISA test for antimeningococcal IgG and IgM antibodies: application to epidemiology and diagnosis; Department of Medical Microbiology, University Hospital Tromso, NorwayWe have developed an enzyme-linked immunosorbent assay (ELISA) in order to quantitate antimeningococcal IgM and IgG serum antibodies . The B:15 meningococcal strain was used as coating antigen, and class specific antibodies were detected by using alkaline phosphatase labelled rabbit anti-human IgM or IgG as conjugate . The specific IgG activity was higher in sera from healthy meningococcal carriers than non-carriers, but the difference was not statistically significant . Antimeningococcal IgM serum antibodies were more frequent in carriers that in non-carriers . Acute sera from 34 patients with fulminant meningococcal disease contained less specific IgG and had a higher prevalence of IgM than healthy carriers and non-carriers . By combining measurement of antimeningococcal IgG and IgM antibodies in both acute and convalescent sera 15/18 meningococcal patients demonstrated an increase in either IgG and IgM antibodies during the hospital stay, giving a sensitivity of 83% . 8/118 individuals without meningococcal disease had detectable specific IgM antibodies in their serum, giving a clinical specificity of the test of 93% . We conclude that quantitation of specific IgG antimeningococcal antibodies by a whole bacteria ELISA test may be a useful test for the study of immunity against meningococcal disease in single individuals as well as in epidemiological studies . The combined use of the IgG and IgM tests is helpful in the diagnosis of meningococcal disease when blood or cerebrospinal fluid cultures are negative. Eur J Epidemiol, 1992 Jan, 8(1), 114 - 6 Meningococcal disease in Italy in 1989; Stroffolini T et al.; Meningococcal disease in Italy decreased by 13.4% from 1988 to 1989 . The incidence rate was 0.5/100,000 in the general population and 1.3/100,000 in army recruits . The highest proportion of cases (27%) was seen in subjects 5-14 years old . The sex ratio was 1.3 . Forty-four percent of the isolates belonged to serogroup B; 37% belonged to group C . Forty-six percent of the strains were resistant to sulphonamides and 10% were resistant to minocycline; only 4% were resistant to rifampicin . None of the four military cases observed could be attributed to vaccine failure . One secondary case and no coprimary cases were observed among civilians . The shift in prevalence from serogroup C to serogroup B isolates is the most important finding of this study. Ethiop Med J, 1992 Jan, 30(1), 33 - 6 Nasopharyngeal carriage of Neisseria meningitidis among school children at Ijede, Lagos State, Nigeria; Odugbemi T et al.; A total of 639 school children ranging in age from 5 to 15 years were investigated for nasopharyngeal carriage of Neisseria meningitidis in Ijede, Lagos-State, Nigeria . The carriage rate was found to be 6.2% . Of the 40 children from whom meningococci were isolated, 25 (62.5%) were males and 15 (37.5%) were females . Serogrouping of the isolates showed that serogroup C Neisseria meningitidis was isolated with the highest frequency 40%, while serogroups A, B, and W135 had isolation rates of 25.5%, 17.5% and 7.5% respectively . This study has shown that group C Neisseria meningitidis is the prevalent serogroup among school children in the area, which is south of the meningitis belt in Nigeria. Microb Pathog, 1992 Jan, 12(1), 19 - 26 Anti-idiotype induced protection against Neisseria meningitidis serogroup C bacteremia; Westerink MA et al.; We have developed a monoclonal anti-idiotypic antibody, designated 6F9, which acts as the surrogate image of the meningococcal group C capsular polysaccharide (MCP) . Murine immunization with 6F9 results in a T-dependent anti-MCP antibody response . To examine the protective nature of the antibody response elicited by 6F9 we performed a series of live challenge studies using a murine model for meningococcal infection in which mice were iron dextran treated and challenged with 10 x LD50 of meningococcal group C strain 35E . Adult BALB/c mice immunized with 6F9 had a 100% survival and a significantly reduced level of bacteremia at 24 h . Mice immunized with MCP had an 80% survival rate, all survivors were bacteremic at 24 h . Neonatal mice primed within 24 h of birth and immunized at 4 weeks of age with 6F9 had a 100% survival and cleared their bacteremia by 8 h, which was significantly faster than the MCP primed and immunized mice . Neonatal mice primed with 6F9 and challenged at 5 weeks of age had a survival rate of 90% which was significantly higher than mice primed with MCP and the control group (60% and 50% survival, respectively) . Mice primed at birth and immunized at 8 days had a 100% survival and 90% of these mice had sterile blood cultures by 8 h . Mice primed and immunized with MCP all remained bacteremic at 24 h . These data indicate that the anti-Id 6F9 which mimics the capsular polysaccharide of group C meningococci is capable of inducing protective immunity in immunologically mature as well as immature animals. Immunodefic Rev, 1992, 3(2), 123 - 47 Inherited deficiencies of the terminal components of human complement; Wurzner R et al.; The particularly frequent occurrence of terminal complement deficiencies in patients with Neisserial infections suggests that the cytolytic activity of the complement system is important in resistance to Neisseria meningitidis . There are, however, geographical differences in the prevalence of terminal complement deficiency in patients with meningococcal disease . The data available suggest that either recurrent infection or infection with uncommon serogroups should alert the clinician in Western countries whereas recurrent disease is the important indicator in high risk endemic or epidemic areas . An association of terminal complement deficiencies with susceptibility to autoimmune diseases or non-Neisserial infections is doubtful . For a better understanding of complement deficiencies in relation to disease more accurate characterization of the defects involved will be helpful . Sensitive ELISA techniques and molecular biological assays will be needed . Thus it has been established that two types of deficiencies exist (at least for C6, C7 and C8): one with low but detectable amounts of the component and the other with a complete absence of the protein in question . The subtotal variety appears to show less association with Neisserial infection . Low amounts of functional terminal complement activity may be sufficient for many of its biological functions, suggesting that there is a wide "safety margin". Immunology, 1992 Jan, 75(1), 10 - 6 Properties of a low molecular weight complement component C6 found in human subjects with subtotal C6 deficiency; Orren A et al.; A sensitive ELISA assay was used to quantitate serum complement component C6 concentrations . Levels in the range 0.3-3 micrograms/ml were measured in samples from eight individuals (four separate pedigrees) and two subjects with subtotal combined C6/C7 deficiency who have been reported previously . We defined C6 levels in this range as subtotal C6 deficiency (C6SD) . In contrast, C6 deficiency with levels below 0.03 micrograms/ml was defined as C6Q0 . C6Q0 has been found in 29 unrelated cases which have already been reported . Investigations of the properties of the C6 found in the C6SD subjects showed it to be haemolytically active and able to incorporate into the terminal complement complex . The protein had a relative molecular weight (Mr) of approximately 86% of normal C6 and this Mr was identical to that of the C6 of one combined deficient subject . The Mr of the C6 of the other combined deficient subject was previously estimated as 79% of the Mr of normal C6 . Isoelectric focusing (IEF) analysis with band development by haemolytic overlay revealed that all C6SD samples produced an identical weak C6 band pattern anodal to normal C6A bands . The C7 IEF patterns of the two combined deficient subjects were identical, and the C6 IEF patterns of both were identical to those of the C6SD subjects . Thus the C6 of the combined deficient subjects is probably the same abnormal protein found in the C6SD individuals . None of the C6SD or combined deficient subjects have had meningococcal disease and it may be that low C6 levels afford some protection. Vaccine, 1992, 10(10), 691 - 8 Development and phase 1 clinical testing of a conjugate vaccine against meningococcus A and C; Costantino P et al.; A conjugate vaccine against meningococcus A and C was prepared using the non-toxic mutant of diphtheria toxin CRM 197 as a carrier protein . Capsular polysaccharides of Neisseria meningitidis group A and C were hydrolysed and the resulting oligosaccharides were then coupled to CRM 197 in order to obtain conjugates with a carbohydrate content of 25-30% . The final vaccine that contained 11 micrograms of each oligosaccharide and 88 micrograms of CRM 197 was used to immunize mice and rabbits . After the preclinical studies which showed that the vaccine was safe and immunogenic in animal models, a pilot phase 1 clinical trial, blind versus placebo, was performed on adult volunteers . The difference between the incidence of adverse reactions associated with vaccine and placebo administration was not statistically significant . All the volunteers who received the vaccine had a significant increase in antibodies to group A and C meningococcal capsular polysaccharides after the first dose. Scand J Infect Dis, 1992, 24(3), 333 - 8 Incidence, serogroups and case-fatality rate of invasive meningococcal infections in a Swedish region 1975-1989; Berg S et al.; In a retrospective study of invasive meningococcal infections in Greater Gothenburg, Sweden, 213 cases of culture-verified meningitis or septicaemia were identified during the 15-year period 1975-1989 . The annual incidence was 2.0/100,000 . Cases were seen in all age-groups with the highest rates in the 0-4 and 15-19 year-old groups, 9.5 and 6.2/100,000 respectively . 20% of the patients were less than 2 years . 91% of the patients had no known risk factors . In only 10 cases (5%) was contact with another case of meningococcal infection known . The main clinical manifestations were meningitis (57%), septicaemia with no sign of focal infection (25%) and septic shock (17%) . The case-fatality rate for all the patients was 6.6% and did not change during the 15-year period . One-third of the patients who presented with septic shock died . The serogroup was known for strains from 192 patients . 51% of the strains belonged to serogroup B, 10% to group A and 23% to group C . In conclusion, the incidence of meningococcal infection was low but the relatively high case-fatality rate warrants a search for effective prophylaxis . About 30% of the cases were potentially preventable by the currently available tetravalent (A, C, Y and W135) polysaccharide vaccine, which is immunogenic in children greater than 2 years . Widespread use of antibiotic prophylaxis to close contacts of known cases would not lower the incidence markedly. Zh Mikrobiol Epidemiol Immunobiol, 1992, (7-8), 30 - 4 {The antibody response of animals to a corpuscular meningococcal group-B preparation with different methods of immunization}; Aleksakhina NN et al.; As revealed in animal experiments, the formation of antibodies to group-B N . meningitidis antigens (group-specific polysaccharide, lipopolysaccharide and outer membrane proteins) in response to administration of meningococcal corpuscular preparations depends on the method of administration, the dose, and the number of administrations . In the sera of rabbits, immunized orally, antibodies to all three antigens in sufficiently high titers have been detected. Zh Mikrobiol Epidemiol Immunobiol, 1992, (5-6), 37 - 41 {The type subtyping of meningococci by means of whole-cell immunoenzyme analysis}; Demina AA et al.; In this work the method of the whole-cell enzyme immunoassay, used for the serotype-subtyping of meningococci by means of specific monoclonal antibodies, is described . High specificity of the method, the simplicity of the assay procedure and evaluation of its results, as well as the availability of this method for practical use, have been demonstrated . The results of this investigation confirm the importance of the evaluation of type-subtype appurtenance of reference and laboratory strains used in experiments . Study of 72 meningococcal strains obtained from patients has revealed their polyclonal character in respect of their type-subtype signs. Ann Trop Paediatr, 1992, 12(2), 149 - 54 Prognostic factors influencing mortality in meningococcal meningitis; Fakhir S et al.; The clinical features and some laboratory parameters of 247 cases of meningococcal meningitis admitted between January 1983 and April 1990 to a paediatric ward in Jawahar Lal Nehru Medical College Hospital, India were analyzed retrospectively . A total of 189 (76.5%) were more than 5 years of age . The maximum number of cases occurred between October and April each year . Complications included bleeding tendencies, neurological deficits, gangrene of limbs, arthritis, uveitis and cataract . The overall mortality rate was 16% . A scoring system based on some clinical characteristics correctly predicted a fatal outcome in all but three children. Vaccine, 1992, 10(3), 159 - 63 Murine cross-reactive T-cell epitopes of Neisseria meningitidis outer membrane proteins; Lifely MR et al.; Five non-covalent vaccines of outer membrane proteins (OMPs) complexed to capsular polysaccharide were prepared from Neisseria meningitidis serogroup B strains . Each vaccine contained distinct serotype (class 2/3) and subtype (class 1) OMPs . The cross-reactivity of the T-cell response to the meningococcal vaccine-associated proteins was examined in an in vitro T-cell proliferative assay, following antigenic priming of mice with one of these vaccines (MB6:P1.6) or with its purified class 1 (subtype P1.6) and class 2 (serotype 6) proteins . Cross-reactive T-cell epitopes were found in all five vaccine preparations on both the class 1 and class 2/3 OMPs . Priming of mice with the subtype P1.6 N-terminal peptide led to a significant but small increase in T-cell proliferation with the MB6:P1.6 vaccine. J Infect Dis, 1992 Jan, 165(1), 53 - 68 A comparison of the variable antigens expressed by clone IV-1 and subgroup III of Neisseria meningitidis serogroup A; Achtman M et al.; Serogroup A Neisseria meningitidis of subgroup III has caused two pandemics of meningococcal meningitis since 1966 and recently spread to East Africa . The last epidemics in West Africa in the early 1980s were caused by clone IV-1 . Surface antigens of clone IV-1 strains from West Africa and subgroup III strains from both pandemic waves were analyzed . Lipopolysaccharide was stable within clone IV-1 but variable in subgroup III . Pili from clone IV-1 possessed class I epitopes, while those from subgroup III also possessed class IIa epitopes . Certain class 5 protein variants were expressed by both bacterial clones, possibly reflecting either inheritance of primeval genes or horizontal transmission . Exposure of Gambians to clone IV-1 bacteria stimulated production of bactericidal antibodies cross-reactive with subgroup III bacteria in some individuals but of type-specific antibodies in others . Gambians without bactericidal antibodies usually became healthy carriers rather than developing meningococcal disease on exposure to virulent meningococci. Zh Nevropatol Psikhiatr Im S S Korsakova, 1992, 92(2), 39 - 41 {Status of cellular immunity in viral, serous and meningococcal meningitis}; Zaplotnaia AA; The paper is concerned with the immunological status of 62 patients with meningococcal and viral serous meningitides . A noticeable inhibition of cellular immunity, more pronounced in the CSF was detected . A correlation was shown to exist between the level of humoral factors that block T lymphocyte receptors in the CSF and the disease gravity. Scand J Infect Dis, 1992, 24(3), 323 - 32 DNA fingerprinting in the epidemiology of African serogroup A Neisseria meningitidis; Bjorvatn B et al.; The restriction endonuclease (RE) technique was used to compare 172 meningococcal group A strains collected between 1969 and 1990, mainly from countries of the so-called African Meningitis Belt, the Gambia and Ethiopia . The 64 strains from various African countries (Niger, Chad, Burkina Faso, Cameroon, Morocco, Djibouti) were distributed within 3 main restriction enzyme patterns (REPs); the 77 Gambian strains fell into 5 REPs and the 24 Ethiopian strains into 2 such patterns . Several of the main REPs were formed by clusters of closely related clones . Clones, very similar to dominating REPs of the 1960s in Niger, Burkina Faso and Cameroon, were in the 1980s found to be strongly represented in the Gambia to the extreme west of the Meningitis Belt . One of the Gambian clones from 1983-86 was identical to an Indian clone recovered in New Delhi 1986-87 . Another clone was detected in 1983 in the Gambia, in 1989 again in the Gambia as well as in Ethiopia, and in 1990 in Tanzania . Our results are largely in line with those of previous studies based on modern techniques of protein and isoenzyme electrophoresis . The RE method is useful mainly for the exact genotypic differentiation of closely related clones, and seems to be a valuable complement to phenotypic tools for epidemiological mapping of Group A meningococcal infection. Zh Mikrobiol Epidemiol Immunobiol, 1992, (11-12), 27 - 30 {The evolution of meningococcal infection in Mongolia}; Tsend N et al.; On the basis of the generalization and analysis of the results of bacteriological and immunological investigations the epidemic process of meningococcal infection (MI) in Mongolia was found to undergo definite changes during the last 20 years . Group A meningococci prevailing in the etiology of MI were replaced by strains belonging to group B affecting mainly young children (aged up to 3 years) . MI morbidity rate caused by group B meningococci was found to be higher in Mongolia than in other countries of the world . These data substantiate the necessity of using more effective remedies for the control of this infection and, in particular, specific immunization with vaccines against group B meningococci; profound study of the properties of the circulating meningococcal strains is to be carried out. Ann Med Interne (Paris), 1992, 143 Suppl 1, 13 - 6 Removal of circulating tumor necrosis factor . Its role in septic shock treatment; Janbon B et al.; The tumor necrosis factor (TNF) is a polypeptide secreted by macrophages in response to endotoxins, especially from Gram-negative bacteria . Previous investigations suggest that TNF plays a prominent role in septic shock and meningococcal disease toxicity . A positive correlation was found between the initial serum TNF level and the patient's outcome . Despite the progress made in intensive care management and antibiotic therapy, the prognosis of septic shock remains very poor . Because of the implication of TNF in the pathogenesis of septic shock, we suggest that neutralization or elimination of this cytokine by plasma or blood exchanges could contribute to the treatment of severe forms of this syndrome . Five plasma exchanges and two blood exchanges were performed in 6 patients admitted for septic shock or purpura fulminans . Serum TNF levels were measured by immunoradiometric assay (Medgenix, ERIA Pasteur) before and after exchange . Serum TNF levels were found to be decreased by an average of 62% after the exchange . We conclude that exchange therapies are efficient in removing plasma TNF . Nevertheless, because of the limited number of patients treated, it is not possible to evaluate the clinical efficacy of such techniques. Ugeskr Laeger, 1991 Dec 16, 153(51), 3613 - 4 {Chronic meningococcemia . A review and a report of 4 cases}; Rasmussen LH et al.; Four cases of chronic meningococcacemia (CM) are described . The diagnosis was based on recurring fever, exanthema, arthralgia/arthritis and positive blood culture with Neisseria meningitidis . The meningococcal antibody-test (MAT) was positive in all of the three patients tested . None of the patients had positive throat culture for Neisseria meningitidis . All patients had leucocytosis during the febrile periods . The symptoms lasted for 5-150 days before the diagnosis was made . These findings are discussed in relation to the literature. Infect Immun, 1991 Dec, 59(12), 4349 - 56 Specificity of antibodies to O-acetyl-positive and O-acetyl-negative group C meningococcal polysaccharides in sera from vaccinees and carriers; Arakere G et al.; Most group C Neisseria meningitidis strains produce an O-acetyl-positive polysaccharide, a homopolymer of alpha-2----9-linked N-acetylneuraminic acid with O-acetyl groups at the C-7 and C-8 of its sialic acid residues . The majority of disease isolates have been reported to contain this polysaccharide . Some strains produce group C polysaccharide lacking O-acetyl groups . The licensed vaccine contains the O-acetyl-positive polysaccharide . We have measured the antibody specificities to the two polysaccharides in sera from asymptomatic group C meningococcal carriers and vaccinated adults by a new enzyme-linked immunosorbent assay (ELISA) procedure using methylated human serum albumin for coating the group C polysaccharide onto microtiter plates . Inhibition of binding of serum antibodies to polysaccharide-coated plates was measured by ELISA after incubation with O-acetyl-positive and O-acetyl-negative group C polysaccharides . Greater inhibition of binding of carrier sera was observed with the homologous polysaccharide . There was substantial inhibition of binding of vaccinee sera to the O-acetyl-positive polysaccharide-coated plate following preincubation with O-acetyl-positive polysaccharide, but homologous inhibition on plates coated with the O-acetyl-negative polysaccharide required much higher concentrations of polysaccharide . Carrier sera may have a higher proportion of antibodies with greater specificity for the O-acetyl-negative polysaccharide, while vaccinee sera contain antibodies with greater affinity for the O-acetyl-positive polysaccharide . Studies with monoclonal antibodies specific for O-acetyl-positive and O-acetyl-negative polysaccharides reveal that the percentage of group C meningococcal disease caused by O-acetyl-negative strains remains about 15%, as found over 15 years ago. NIPH Ann, 1991 Dec, 14(2), 95 - 101; discussion 101-2 The Norwegian meningococcal group B outer membrane vesicle vaccine: side effects in phase II trials; Nokleby H et al.; In order to establish the safety of the Norwegian meningococcus B vaccine we have focused on detailed reporting of side effects in several phase II trials . We report here the results of the largest single phase II study, (step II-6) including 877 school children . The incidence of local side effects was significantly higher in the vaccine than in the placebo group, but most of them were mild and short-lasting . Mild systemic side effects were commonly reported in both groups, but more severe side effects were rare and almost equally distributed between the groups. NIPH Ann, 1991 Dec, 14(2), 81 - 91; discussion 91-3 Design of clinical trials with an outer membrane vesicle vaccine against systemic serogroup B meningococcal disease in Norway; Bjune G et al.; An outer membrane vesicle vaccine against acute, systemic disease caused by meningococci of serogroup B has been developed . The vaccine has been tested consecutively in phase I and phase II clinical trials including more than 5000 volunteers . These trials provided data on safety, immunogenicity and reactogenicity and possible effect on carriage of meningococci in the throat, and consequently formed the basis for two major protection trials; one in secondary school students and one among military recruits . The aims, design and major results of phase I and phase II studies are described as well as the design and organization of the protection trials. NIPH Ann, 1991 Dec, 14(2), 67 - 79; discussion 79-80 Production, characterization and control of MenB-vaccine "Folkehelsa": an outer membrane vesicle vaccine against group B meningococcal disease; Fredriksen JH et al.; A vaccine against serogroup B meningococcal disease has been prepared from a B:15:P1.7,16 meningococcal strain (44/76) by fermentor growth and extraction of the bacteria with the detergent deoxycholate . Outer membrane vesicles (OMV) were purified by ultracentrifugation and adsorbed to aluminium hydroxide adjuvant . OMV contained the major class 1, 3, 4 and 5 proteins and some minor high molecular weight protein components . Relative to protein, the vaccine also contained about 8% phospholipid, 7% lipopolysaccharide and 16% deoxycholate . The product was generally non-pyrogenic to humans in ordinary doses and was highly immunogenic in mice and humans . Production and control steps, physical, chemical and immunological data for the vaccine are described. NIPH Ann, 1991 Dec, 14(2), 57 - 65; discussion 65-6 The epidemiology of meningococcal disease in Norway 1975-91; Lystad A et al.; The epidemiology of meningococcal disease (MCd) in Norway is described on the basis of official notification figures for 1975-91 . Morbidity is presented by serogroup of the isolated Neisseria meningitidis strain, time of onset of the disease in addition to the place of living, age and sex of the patient . A long-term group B epidemic with high incidence and case fatality rates in the age groups below 5 years and between 13 and 19-20 years is the main characteristics of the situation. NIPH Ann, 1991 Dec, 14(2), 225 - 30; discussion 230-1 Development of a second generation group B meningococcal vaccine; Frasch CE et al.; Outer membrane protein vaccines have now been demonstrated to be effective in prevention of group B Neisseria meningitidis disease, but the extent and duration of protection needs improvement . To develop a second generation outer membrane protein vaccine we have begun studies to evaluate vaccines containing iron regulated proteins in lipopolysaccharide depleted outer membrane vesicles . Since the iron regulated proteins are critical for in vivo survival, it is our working hypothesis that antibodies to these proteins will either be bactericidal or block iron uptake . Four representative strains were selected, and preliminary studies indicate that vaccines containing the iron regulated proteins are immunogenic in mice. NIPH Ann, 1991 Dec, 14(2), 219 - 21; discussion 222-4 Vaccine efficacy determination; Broome CV; The "Gold standard" in vaccine testing is the randomized, placebo controlled, double-blind efficacy trial . Once a protective immune mechanism is defined, e.g., from an efficacy trial, vaccine performance can then be judged by serologic parameters . Although immunogenicity studies can provide important information, in many instances the answer has to come from efficacy trials . For rare diseases like meningococcal disease, these trials are expensive and difficult to conduct . It is therefore incumbent to learn as much as possible from each trial . Issues in pre-licensure studies include: vaccine selection, site selection, trial design, assignment to treatment and control groups, definition and surveillance for endpoints (cases, adverse reactions), identification of surrogate markers for protection, and utilization of monitoring committees. NIPH Ann, 1991 Dec, 14(2), 195 - 207; discussion 208-10 Vaccine against group B Neisseria meningitidis: protection trial and mass vaccination results in Cuba; Sierra GV et al.; The Cuban vaccine, first in the world with proven efficacy against group B-caused disease, is based on outer membrane proteins from B meningococci capable of inducing long-lasting and high-titered bactericidal antibodies in humans . This bactericidal activity has a wide spectrum against all pathogenic group B Neisseria meningitidis tested . A randomized, double-blind controlled trial of the vaccine efficacy was performed during 1987-1989 with 106,000 10-14 years old students from 197 boarding schools in seven provinces . The efficacy obtained was 83% (chi 2, p less than 0.002; Fischer exact, p less than 0.001) . In a second field trial including 133,600 persons from 5 months to 24 years of age in Ciego de Avila province (30 cases/10(5) inhabitants, the highest incidence rate in Cuba) by comparing vaccinated and non-vaccinated population after 2.5 years of observation and careful follow-up, the efficacy and safety was confirmed . Because of these results and because of the very low reactogenicity of the vaccine, the Ministry of Public Health took the advice of the Scientific Council to vaccinate all children between 3 months and 6 years of age in the most affected provinces . No severe or long lasting reactions to the vaccine were observed after the millions of doses administered . The efficacy of vaccination varied in the provinces between 83% and 94%, among age groups ranging from 3 months and 20 years . After 3 years of massive application no severe reactions occurred and one of the most severe epidemics has been practically eradicated. NIPH Ann, 1991 Dec, 14(2), 157 - 65; discussion 166-7 Serum opsonins to serogroup B meningococci after disease and vaccination; Halstensen A et al.; In this review the results of three previous studies are compared and discussed . Sera from 101 patients with meningococcal disease and from 113 volunteers immunized twice with vaccine preparations against serogroup B meningococci were examined for antimeningococcal opsonic activity using a chemiluminescence (CL) method . Twelve groups of vaccinees were immunized twice with one of four different doses of an outer membrane vesicle (OMV) preparation either alone or complexed to serogroup C polysaccharide and/or the adjuvant Al(OH)3 . The OMV vaccine strain (44/76) was a patient isolate characterized as B:15:P1.16 . The 89 surviving patients and 97/113 volunteers responded with significantly increased opsonic activity to the vaccine strain . Sera from all vaccinees with low preimmunization levels demonstrated a significant postimmunization increase in opsonic activity . The vaccine response was dose related, and the second injection induced a booster response in those who received preparations containing Al(OH)3 . At 26 weeks a reduction in opsonic activity to preimmunization levels was noted in 19/97 previous responders . The reduction was less pronounced in those who were immunized with the higher doses . Using CL and flow cytometry we found vaccinee sera to show cross reacting opsonin responses to other serogroups and serotypes of meningococci except meningococci of serotype 2a and 2b . The increase in antimeningococcal opsonins after vaccination suggests that the serogroup B OMV vaccine may induce protection against clinical disease. NIPH Ann, 1991 Dec, 14(2), 147 - 55; discussion 155-6 Bactericidal antibodies after vaccination with the Norwegian meningococcal serogroup B outer membrane vesicle vaccine: a brief survey; Hoiby EA et al.; Results from the serum bactericidal assay (BA) after immunization of human volunteers with the Norwegian serogroup B meningococcal outer membrane vesicle vaccine are surveyed . In the phase II trials with adults we found very high seroconversion rates (greater than 98%) against the vaccine strain in the BA . Details in the antigenic composition of the inoculum used in the BA seem very important as shown here by finding lower bactericidal titres with teenager sera when tested with a variant of the standard inoculum . The present preliminary report corresponds to the presentation given at the Report Meeting on the Norwegian Meningococcal Vaccine Trial, Oslo, 12 September, 1991. NIPH Ann, 1991 Dec, 14(2), 125 - 30; discussion 130-2 Results of an efficacy trial with an outer membrane vesicle vaccine against systemic serogroup B meningococcal disease in Norway; Bjune G et al.; A placebo controlled, double blind efficacy trial with a new outer membrane vesicle vaccine against systemic meningococcal disease of serogroup B, has been conducted in Norwegian secondary schools . The study was randomized at school level (1335 schools) and 171,800 students volunteered . The study started in October 1988 and the code was opened in June 1991 . Out of the thirty-six proven cases of acute, severe, systemic disease caused by serogroup B meningococci among the participants, twelve occurred in eleven schools given vaccine, twenty-four in twenty-four schools given placebo . twenty-four cases were recorded among secondary school students who did not participate in the study . The protection rate was calculated to 57.4% with a p-value of 1.2% and lower limit of confidence (95%) to 27.7% . The results have initiated research towards an improved outer membrane vesicle vaccine against this disease. NIPH Ann, 1991 Dec, 14(2), 107 - 21; discussion 121-3 The Norwegian meningococcal serogroup B outer membrane vesicle vaccine protection trials: case tracing, meningococcal antigen detection and serological diagnosis; Hoiby EA et al.; A survey is given of the efforts made to inform the general public, the potential vaccinees and their parents, and the health care personnel about meningococcal disease in general and the vaccination trial in particular, as a preparation for the meningococcal outer membrane vesicle serogroup B vaccine (MenB-vaccine "Folkehelsa") trials in secondary school students and military conscripts in Norway . Our case reporting system, supplementing the official notification, concerning even vaguely suspected cases in the age cohorts involved, is described . The efforts made to collect clinical material as well as laboratory and clinical data from 221 registered suspected cases are delineated . We also briefly summarize our cerebrospinal fluid antigen detection methods and diagnostic meningococcal serology work on these suspected cases . The compiled information on findings done at the admitting hospital of the possible cases and the additional diagnostic data provided at the National Institute of Public Health were put at the disposal of the independent Diagnosis Review Committee (DRC) as a basis for their diagnostic decisions before code opening for the meningococcal serogroup B outer membrane vesicle vaccine protection trial 3 June 1991. Microb Pathog, 1991 Dec, 11(6), 447 - 52 Blocking of bactericidal killing of Neisseria meningitidis by antibodies directed against class 4 outer membrane protein; Munkley A et al.; The class 4 protein of Neisseria meningitidis is a highly conserved outer membrane protein, closely related to the protein PIII of Neisseria gonorrhoea . Monoclonal antibodies SM50 and SM54 raised against PIII also react with class 4 protein but do not promote complement mediated bactericidal killing of meningococci . In addition, mAb SM50 inhibits the anti-meningococcal bactericidal activity both of normal human sera and of mAb SM300, directed against a protective epitope on the class 1 outer membrane protein . The ability of class 4 protein to induce such 'blocking' antibodies suggests that its presence in experimental vaccines, based on meningococcal outer membranes, may be antagonistic to the development of effective bactericidal immunity. Am J Trop Med Hyg, 1991 Dec, 45(6), 676 - 82 Detection of IgM antibodies to Neisseria meningitidis group A polysaccharide in meningitis patients by direct and antibody capture enzyme-linked immunosorbent assays; Sippel JE et al.; Serum specimens obtained from culture-positive group A meningococcal meningitis patients in Cairo, Egypt were tested for immunoglobulin M (IgM) antibodies to Neisseria meningitidis group A polysaccharide by direct and IgM capture enzyme-linked immunosorbent assays (ELISAs) . Sera from patients with meningitis caused by other bacteria were used as negative control specimens . The IgM antibodies to this antigen were detected by direct ELISA in 93% of 58 specimens obtained from patients with group A meningococcal disease three or more days after hospital admission, and by IgM capture ELISA in 83% of 60 such specimens . Sixteen percent of 25 specimens obtained three or more days after admission from negative control patients were positive by direct ELISA, and 4% were positive by IgM capture ELISA . The correlation coefficient of the results with the two assays was 0.85. J Trauma, 1991 Dec, 31(12), 1693 - 5 Posttraumatic meningococcal meningitis: case report; Stillwell M et al.; A case is described of fulminant meningococcal meningitis occurring 1 day after serious head and facial trauma . Although meningococcus is one of the most common causes of bacterial meningitis in general, it is distinctly rare as a cause of posttraumatic meningitis . A review of the literature is included. NIPH Ann, 1991 Dec, 14(2), 169 - 79; discussion 180-1 Human antibody responses after vaccination with the Norwegian group B meningococcal outer membrane vesicle vaccine: results from ELISA studies; Rosenqvist E et al.; Antibody responses after vaccination with three different formulations of a new meningococcal group B outer membrane vesicle (OMV) vaccine have been studied with the ELISA technique using four different antigens . Sera from about 1200 vaccinees participating in steps 1, 2, 3 and 6 of the phase II clinical trials in Norway were analysed . The effects of non-covalently complexing the OMV antigen to group C polysaccharide (C-PS) and of adsorbing OMV (with and without C-PS) to aluminium hydroxide (AH) were studied . All three vaccine formulations were highly immunogenic in humans . Adsorption of the vaccine to AH had a relatively small effect on the immune response, but the results indicated that the booster response was stronger with the adsorbed than with the unadsorbed vaccines . Some increase in the immune response against OMV was also observed by non-covalent complexing OMV with C-PS, particularly after the second dose . In most of the vaccinees the antibody levels were significantly reduced 6 to 12 months after vaccination . Adsorption of the vaccine to AH had no effect on the antibody response against C-PS . Comparison with bactericidal activity of the same sera was done . A highly significant correlation was observed between the bactericidal titres and the levels of IgG antibodies against OMV and class 5C protein, whereas the correlation between antibody levels against lipopolysaccharide and the bactericidal activity was poor. Med J Aust, 1991 Nov 18, 155(10), 713 - 4 Severe meningococcal septicaemia associated with splenic rupture; Buist MD et al.; OBJECTIVE: To present the first report of ruptured spleen associated with meningococcal septicaemia . CLINICAL FEATURES: A 13-year-old girl presented with an acute abdomen and clinical signs of meningococcal septicaemia . Features of her illness placed her in a high mortality group . INTERVENTION AND OUTCOME: She required cardiovascular and respiratory support in the Intensive Care Unit . Failure to initially identify the organism led to percutaneous fine-needle aspiration of fluid in the lesser sac . A laparotomy revealed free intraperitoneal blood and a ruptured spleen . During the course of her illness she was given penicillin and methylprednisolone, and required haemodialysis . She made a complete recovery . CONCLUSION: Ruptured spleen does occur with severe meningococcaemia, and may complicate management. Lancet, 1991 Nov 2, 338(8775), 1093 - 6 Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway; Bjune G et al.; For more than 15 years, Norway has had the highest incidence of meningococcal disease in northern Europe, with 80% of cases being due to serogroup B meningococci . The case-fatality has remained high, at about 10% . In this study, an outer membrane vaccine, which had previously been shown to induce an increase in bactericidal antibodies to the parent strain, was assessed in a large-scale, randomised, double-blind trial . From October, 1988, 171,800 students in secondary schools volunteered to take part in a double-blind, placebo-controlled, efficacy trial with school as the randomisation unit . Hospitals and clinics that routinely receive patients with infectious disease were asked to report urgently all cases of suspected meningitis and/or septicaemia in 13-21-year-old students in Norway . These cases were registered and further investigated according to a detailed protocol . 89 out of the 221 cases investigated by June 3, 1991, were shown to be severe systemic disease due to group B meningococci . 36 cases in 35 schools took part in the trial (11 schools with vaccinated students and 24 with students given placebo) . The calculated rate of protection was thus 57.2% (p = 0.012, one-sided test) . The findings suggest that, although the vaccine conferred protection against group B meningococcal disease, the effect was insufficient to justify a public vaccination programme. APMIS, 1991 Nov, 99(11), 965 - 71 Granulocyte functions and Neisseria meningitidis: influence of properdin-deficient serum; Soderstrom C et al.; Granulocyte-mediated reactions such as opsonization, chemotaxis, and release of granulocyte myeloperoxidase and lactoferrin were studied in properdin-deficient and normal human serum incubated with serogroup A and W-135 meningococci . There were no differences between the sera when serogroup A meningococci were studied . Opsonic and chemotactic activity were impaired against serogroup W-135 meningococci in properdin-deficient serum . Restitution with properdin restored both activities . We found similar release of myeloperoxidase and lactoferrin from granulocytes challenged with serogroup A or W-135 meningococci in either sera . These findings are in accordance with the clinical observations of meningococcal infections caused by serogroup W-135 in properdin-deficient patients as well as the absence of infections caused by serogroup A meningococci. Zh Mikrobiol Epidemiol Immunobiol, 1991 Nov, (11), 14 - 7 {The effect of the nature of the strain on the character of the production of iron-dependent proteins by meningococci}; Gorbacheva BO et al.; The comparative study of three Neisseria meningitidis strains (15, 125, 2394) was carried out by the method of electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate and by the method of immunoblotting . The intensive expression of 8 iron-regulated proteins (IRP) was shown to occur in iron-deficient culture medium . The major IRP with a molecular weight of 35 kD was expressed by all above-mentioned N . meningitidis strains under the conditions of iron deficiency and cross-reacted with 10 mouse and rabbit antisera to N . meningitidis of different groups, i.e . it was common to all Neisseria species . The antigenic activity of various IRP essentially differed with respect to antisera of animals and sera of patients with meningococcal infection. J Clin Microbiol, 1991 Nov, 29(11), 2489 - 93 Emergence of a virulent clone of Neisseria meningitidis serotype 2a that is associated with meningococcal group C disease in Canada; Ashton FE et al.; Multilocus enzyme electrophoresis was used to characterize 378 isolates of Neisseria meningitidis serogroup C recovered during a period of an increase in group C meningococcal disease in Canada . Thirty-four enzyme electrophoretic types were found among the isolates, which were predominantly (96.0%) serotype 2a . One clone (ET 15), characterized by a rarely occurring allele for the enzyme fumarase, was responsible for a focal outbreak in Ontario followed by the spread of group C disease across the province . This clone, which occurred infrequently among strains isolated in 1986, accounted for over 65% of group C strains associated with meningococcal disease in Canada in 1990. Arch Dis Child, 1991 Nov, 66(11), 1296 - 9 Deficiency of prostacyclin production in meningococcal shock; Heyderman RS et al.; A deficiency of prostacyclin (PGI2) production by the vascular endothelium might underline the severe vasoconstriction and intravascular thrombosis that characterise meningococcal shock . The effect on PGI2 synthesis by human umbilical vein endothelial cells (HUVEC) in culture was examined in sera from children with meningococcal shock, healthy adults, and children with other febrile illnesses . In comparison with adult controls, PGI2 synthesis was reduced when HUVEC were incubated with the sera from 10 of 13 patients with meningococcal shock . A similar defect was observed with only four of 20 sera from children with other febrile illnesses . The effect of sera from patients with meningococcal shock on HUVEC was reversible with normal serum, and seems to be due to the absence of a factor necessary for PGI2 production rather than an inhibitor . These findings suggest that a deficiency of PGI2 may have a role in the pathogenesis of meningococcal shock and that exogenous PGI2 may be of therapeutic benefit. Mol Immunol, 1991 Nov, 28(11), 1193 - 200 The influence of the adjuvant Quil A on the epitope specificity of meningococcal lipopolysaccharide anti-carbohydrate antibodies; Verheul AF et al.; Rabbits were immunized with immunotype L3,7,9 phosphoethanolamine (PEA) group containing oligosaccharide-tetanus toxoid conjugates both with and without the addition of the adjuvant Quil A . The epitope specificity of the antibodies present in these antisera was analysed in an immunotype L2 and L3,7,9 specific inhibition ELISA using the homologous and heterologous lipopolysaccharide, oligosaccharide and partial dephosphorylated oligosaccharide as inhibitors . Two groups of antisera could be identified . In one group of antisera, at least two antibody populations are present, namely directed against the PEA group containing determinants on immunotype L3,7,9 lipopolysaccharide and against immunotype L2 specific epitopes in which no PEA group is present . In the second group of antisera, one but probably more antibody populations are detected with a similar specificity towards the conserved epitopes of both immunotypes . In general, immunization with the conjugates only resulted in the induction of antibodies against the PEA group containing epitopes on the L3,7,9 lipopolysaccharide (80%) . Antibodies directed against the conserved epitopes of both immunotypes are mainly evoked with the conjugates in combination with the adjuvant Quil A (80%) . Although these results suggest that the epitope specificity of the antibodies induced depends on the use of Quil A, the influence of genetic factors cannot be excluded . At the moment it is not known whether the differences in epitope specificities are reflected in biological function of these antibodies . However, the induction of antibodies with clearly different epitope specificities after immunization of different rabbits with the same antigen stresses the importance of this kind of analysis when developing a vaccine based on oligosaccharide-protein conjugates. Lijec Vjesn, 1991 Nov-Dec, 113(11-12), 384 - 6 {Duration of the Neisseria meningitidis serogroup B serotype 2 carrier state}; Bencic Z et al.; Of 168 examined secondary school children from Zagreb, Neisseria meningitidis, serogroup B, serotype 2 was isolated from the pharynx smear taken from 14 healthy carriers, aged 15-18 . Carriership was observed during the period of 19 months . During that period the pharynx smear was taken four times so that in total there were five samples from each examinee, with the purpose of finding Neisseria . Neisseria meningitidis serogroup B, serotype 2 was isolated and identified by using the standard microbiological methods . Serogroup and serotype were identified by the slide agglutination method, and were used group and type specific antisera . Of 14 identified carriers two persons had continuous duration of carriership of N . meningitidis, serogroup B, serotype 2 during the period of nineteen months . In 6 persons over the period of 9 months, in all five samples of pharynx smear the same meningococcus was identified . This epidemiological study has determined the longest duration of carriership of Neisseria meningitidis serogroup B, serotype 2 described so far in the literature . The role of carriership in the occurrence of the meningococcal disease has not been fully explained. Infect Immun, 1991 Nov, 59(11), 4097 - 102 Insertion of Tn916 in Neisseria meningitidis resulting in loss of group B capsular polysaccharide; Stephens DS et al.; We recently found that the 16.4-kb conjugative transposon Tn916 could be introduced into Neisseria meningitidis by transformation and that it appeared to transpose to many different sites in the chromosome of recipient meningococci . In order to identify transposon-induced alterations of specific meningococcal virulence determinants, a library of meningococcal Tetr transformants containing Tn916 was made and screened for those altered in the production of group B capsular polysaccharide . A capsule-defective mutant, M7, was identified by using monoclonal and polyclonal antisera to group B polysaccharide in immunoblot and agar antiserum procedures . Growth of M7 was similar to that of the parent strain . M7 produced no group B capsular polysaccharide by rocket immunoelectrophoresis, and the mutation was stable during laboratory passage . The capsule-defective phenotype was linked to Tetr, as demonstrated by immunoblot and Southern blot analysis of progeny Tetr transformants (transformants of the parent strain obtained with DNA from M7) . A capsule-deficient mutant, O8, was identified by using a similar approach . Analysis of the Tn916 insertions in M7 and O8 indicated that a significant portion of the transposon on either side of the tetM determinant had been lost . The ability of Tn916 to generate defined, stable mutations in meningococcal virulence determinants is demonstrated by our study. Ugeskr Laeger . 1991 Oct 14;153(42):2955. {Necrotizing fasciitis . A rapid fatal course of Streptococcus pyogenes, Lancefield group A serotype M1 (killer streptococci), infection}; Pedersen HS et al.; The case history of necrotizing fasciitis in a previously healthy man aged 37 years is presented . The disease ran a rapidly fatal course . The only finding on bacterial culture was Streptococcus pyogenes, Lancefield group A, serotype M1, ("killer streptococci") . The therapeutic possibilities are briefly outlined and the importance of rapid surgical intervention is emphasized . It is concluded that this patient was actually beyond therapeutic aid less than 12 hours after admission . Necrotizing fasciitis caused by Streptococcus pyogenes, Lancefield group A, serotype M1, is comparable with meningococcal disease . It appears probable that the disease had developed in this patient as a sequel of streptococcal arthritis. Clin Chem, 1991 Oct, 37(10 Pt 1), 1691 - 5 Radioimmunoassay of interleukin-6 in plasma; Teppo AM et al.; We present a double-antibody radioimmunoassay for determining human interleukin-6 (IL-6) in biological fluids . The detection limit of the assay is 20 ng/L (B0 - 2 SD) . Bound radioactivity in the range of 30% to 90% of the B0 counts corresponds to IL-6 concentrations of 100 to 14,000 ng/L . Analytical recovery of IL-6 added to EDTA-treated plasma averaged 25% more than that added to serum . The plasma concentration of IL-6 was therefore approximately 85 ng/L more than the concentration in simultaneously drawn serum . The mean serum concentration of IL-6 in 45 healthy subjects was 83 ng/L (range 20-290 ng/L), in 20 patients with multiple myeloma 303 ng/L, in 20 patients with rheumatoid arthritis 234 ng/L, and in 13 patients with systemic lupus erythematosus 183 ng/L . Markedly increased (greater than 3000 ng/L) concentrations of IL-6 were found in sera of patients with meningococcus meningitis and infectious peritonitis. Infect Immun, 1991 Oct, 59(10), 3566 - 73 Minimal oligosaccharide structures required for induction of immune responses against meningococcal immunotype L1, L2, and L3,7,9 lipopolysaccharides determined by using synthetic oligosaccharide-protein conjugates; Verheul AF et al.; The 12 types of meningococcal lipopolysaccharide (LPS) (immunotypes) contain immunotype-specific and cross-reactive epitopes situated on the oligosaccharide part of the LPS molecules . To identify useful cross-reactive epitopes and to determine minimal oligosaccharide structures required for the induction of an immune response against the most prevalent immunotypes, L1, L2, and L3,7,9, synthetic as well as native LPS-derived oligosaccharides were conjugated with tetanus toxoid . L3,7,9 phosphoethanolamine (PEA) group-containing oligosaccharide-tetanus toxoid conjugates evoked high immunoglobulin G (IgG) antibody levels in rabbits which were detected by an L2-, L3,7,9-, and, depending on the antiserum, L1-specific enzyme-linked immunosorbent assay (ELISA) . Inhibition studies revealed that an identical antibody population was detected by L1 and L3,7,9 ELISA, indicating a similar tertiary structure of the inner core oligosaccharide of these two immunotypes . These antibodies recognize PEA group-containing epitopes present on the L1 and L3,7,9 LPS . An L2 PEA group-containing oligosaccharide-tetanus toxoid conjugate elicited L2- and L3,7,9-specific IgG antibodies, but in contrast with the L3,7,9 conjugates, no L1-specific IgG antibodies were evoked . These results indicate that L1 and L2 LPS do not contain cross-reactive epitopes, whereas both L2 and L3,7,9 LPS and L1 and L3,7,9 LPS possess common determinants . Three linear oligosaccharides and one branched oligosaccharide, representing partial structures of the inner core oligosacchardes of meningococcal LPS, were synthesized . Only the branched synthetic oligosaccharide-containing conjugate was able to induce and L1- and L3,7,9-specific immune response, whereas the linear oligosaccharide-protein conjugates evoked L2-specific immune responses . The branched oligosaccharide (beta-D-Glcp(1----4)-{L-alpha-D-Hepp(1----3)}-L-alpha-D-Hepp ) is therefore considered a minimal structure required for the induction of an immune response against L1 and L3,7,9 LPS and part of a cross-reactive epitope between these two immunotypes . For L2-specific immune responses, oligosaccharide structures terminating in beta-D-Glcp(1----4), alpha-D-GlcNAcp(1----2), or L-alpha-D-Hepp(1----5) are needed . The results suggest that it is possible to prepare an oligosaccharide structure with the ability to evoke an immune response against L1, L2, and L3,7,9 LPS . A feasible structure for such a "hybrid" oligosaccharide is discussed. Microb Pathog, 1991 Oct, 11(4), 249 - 57 Cloning and expression in Escherichia coli of opc, the gene for an unusual class 5 outer membrane protein from Neisseria meningitidis (meningococci/surface antigen); Olyhoek AJ et al.; A genomic library was constructed in a lambda gt11 vector using chromosomal DNA from a meningococcal serogroup A strain and plaques expressing the class 5C protein were recognized by screening with specific monoclonal antibodies . The opc insert was subcloned into a multicopy plasmid which induced expression of that protein in Escherichia coli as a surface-exposed major outer membrane protein . The nucleotide sequence of opc is typical of an outer membrane protein with a promoter and terminator region, a leader peptide which is cleaved during expression and a complete open reading frame . Unlike other meningococcal class 5 proteins or gonococcal P.II proteins, the sequence did not contain any pentanucleotide repeats and the sequence showed little homology to these other functionally related proteins . However, the predicted amino acid sequence of the mature protein for opc showed 27% similarity to that for a second opa gene cloned from the same meningococcal strain . This is the first report of cloning and expression of a functional meningococcal gene encoding a class 5 outer membrane protein in E . coli. Zh Mikrobiol Epidemiol Immunobiol, 1991 Oct, (10), 55 - 8 {The effect of vaccination on local immunity indices; the determination of antimeningococcal antibodies in saliva}; Martynov IuV et al.; Local immunity characteristics were studied in 130 young males; of these, 80 had been immunized with group A meningococcal vaccine . In nonstimulated saliva, collected prior to vaccination, then on days 7, 14 and 30 after vaccination, the levels of IgA antibodies to group A meningococcal group-specific polysaccharide (PS-A) were determined in the enzyme immunoassay, and secretory IgA and IgA, IgG, IgM were determined by Mancini's method . The study revealed that after the parenteral administration of group A meningococcal vaccine an increase in the concentrations of SIgA and IgA antibodies to PS-A occurred . The manifestation of changes in local immunity characteristics in response to meningococcal vaccine depended on the initial level of IgA antibodies to PS-A. Microbiologica, 1991 Oct, 14(4), 333 - 6 Meningococcal disease in Italy in 1990; Stroffolini T et al.; The incidence of meningococcal disease in Italy in 1990 was 0.5/100,000 in the general population and 0.7/100,000 in army recruits . The highest proportion of cases (32%) was seen in subjects 1-4 years old . The sex ratio was 1.0 Serogroup B constituted 72% of the isolates; 16% belonged to group A and 12% belonged to group C . The proportion of strains resistant to suphonamides was 56%, while no strain was resistant to minocycline or rifampicin . Two secondary cases, but no comprimary cases occurred among civilians . The predominance of serogroup B and the further decline in military cases constitute the findings of major interest. Sex Transm Dis, 1991 Oct-Dec, 18(4), 228 - 32 Neisseria meningitidis in specimens from urogenital sites . Is increased awareness necessary? Hagman M, Forslin L, Moi H, Danielsson D. Neisseria meningitidis serogroups B type 2 and Y were isolated from urogenital specimens from three heterosexual patients . The first patient was a young man with the clinical signs and microscopic findings of a typical gonococcal urethritis . The second was a middle-aged woman with cervicitis, in whom neither Neisseria gonorrhoeae nor Chlamydia trachomatis were demonstrated by culture . In the third patient, a young woman, N . meningitidis was associated with cervicitis, acute salpingitis, and peritonitis . The patients' clinical symptoms responded quickly to antibiotic treatment . Meningococci of the same serogroup/serotype as the index cases were demonstrated in two of the sexual consorts in pharyngeal specimens but not in genitourinary specimens . Orogenital sexual practice seemed to be the most likely route of transmission . During the period of this study (August 1989-March 1990), the three meningococcal strains observed at the authors' laboratory represented 20% of the total number of urogenital isolates of pathogenic Neisseria . A greater awareness of this problem from medical, diagnostic, epidemiologic, and legal viewpoints is therefore needed. FEMS Microbiol Lett, 1991 Oct 1, 67(2), 179 - 85 The class 3 outer membrane protein (PorB) of Neisseria meningitidis: gene sequence and homology to the gonococcal porin PIA; Wolff K et al.; The class 3 protein (PorB) is an important component of the meningococcal outer membrane . The structural gene (porB) encoding the class 3 protein has been cloned using primers suitable for the amplification of the corresponding chromosomal fragment by the polymerase chain reaction (PCR) . The complete nucleotide sequence was determined and predicts a mature protein of 310 amino acids, preceded by a signal peptide of 19 residues . The predicted protein sequence of the class 3 protein exhibits essential structural homology to the gonococcal porin PIA . The class 3 protein encoding gene was expressed in Escherichia coli under the control of an inducible promoter. J Immunol, 1991 Sep 15, 147(6), 1962 - 7 Human IgA1 blockade of IgG-initiated lysis of Neisseria meningitidis is a function of antigen-binding fragment binding to the polysaccharide capsule; Jarvis GA et al.; We have recently shown that human IgA1 can initiate lysis of group C Neisseria meningitidis via the classical C pathway when bound to specific outer membrane proteins, but that IgA1 can also function as a blocking antibody when bound to the polysaccharide capsule of meningococci . In this report, we further characterized IgA1 blockade by examining the effect of IgA1 on IgG-initiated immune lysis of group C meningococci . We purified IgG and monomeric IgA1 from either convalescent group C meningococcal case sera or tetravalent (A, C, Y, W135) polysaccharide vaccinate sera . In the absence of IgA1, IgG initiated complete lysis (greater than 99%) of strains 118V (C:P3,4:L2,4) 126E (C:P3:L1,8), and 35E (C:P5:L2) . Addition of IgA1 to the bactericidal reaction mixture completely blocked the lytic function of IgG . Removal of the Fc portion of IgA1 with either pepsin or IgA1 protease did not affect blockade . Both the F(ab')2 and Fab derivatives of IgA1 blocked lysis quantitatively as well as intact IgA1 . The Fc fragment produced by IgA1 protease cleavage neither increased nor decreased Fab-mediated blockade . IgA1 and its Fab and F(ab')2 fragments blocked IgG-initiated lysis via either the classical pathway in factor B-depleted and in properdin-deficient serum, the alternative pathway in MgEGTA-chelated serum, or both pathways combined . Absorption of the IgA1 and IgG with alum-bound group C polysaccharide completely removed blocking and lytic activity, respectively, indicating that both the blocking IgA1 and the lytic IgG were specific for the group C capsule . Blocking by IgA1 was a linear function of the polysaccharide Ag-binding capacity (ABC) ratio of blocking IgA1 to lytic IgG . Complete blockade was observed at an ABC ratio of 5.5 . At ABC ratios of 3.3 and 4.4, IgA1 affected significant blockade whether added previous to, concurrent with, or subsequent to sensitization of the organisms with IgG . With the use of a C polysaccharide ELISA, we found that the binding of IgA1 to the group C capsule in the presence of IgG exhibited positive cooperativity and therefore that blockade was independent of the ability of IgA1 to directly compete with IgG for binding to epitopes within the group C capsule . We conclude that IgA1, when bound to the group C polysaccharide capsule, can block IgG-initiated lysis of group C meningococci through either the classical or the alternative pathway before or after the organism is exposed to IgG, and that blockade is an Fc-independent event. J Immunol, 1991 Sep 15, 147(6), 2012 - 8 T cell recognition of Neisseria meningitidis class 1 outer membrane proteins . Identification of T cell epitopes with selected synthetic peptides and determination of HLA restriction elements; Wiertz EJ et al.; No vaccine is yet available against serogroup B meningococci, which are a common cause of bacterial meningitis . Some outer membrane proteins (OMP), LPS, and capsular polysaccharides have been identified as protective Ag . The amino acid sequence of the protective B cell epitopes present within the class 1 OMP has been described recently . Synthetic peptides containing OMP B cell epitopes as well as capsular polysaccharides or LPS protective B cell epitopes have to be presented to the immune system in association with T cell epitopes to achieve an optimal Ir . The use of homologous, i.e., meningococcal, T cell epitopes has many advantages . We therefore investigated recognition sites for human T cells within the meningococcal class 1 OMP . We have synthesized 16 class 1 OMP-derived peptides encompassing predicted T cell epitopes . Peptides corresponding to both surface loops and trans-membrane regions (some of which occur as amphipathic beta-sheets) of the class 1 OMP were found to be recognized by T cells . In addition, 10 of 11 peptides containing predicted amphipathic alpha-helices and four of five peptides containing T cell epitope motifs according to Rothbard and Taylor (Rothbard, J . B., and W . R . Taylor . 1988 . EMBO J 7:93) were recognized by lymphocytes from one or more volunteers . Some of the T and B cell epitopes were shown to map to identical regions of the protein . At least six of the peptides that were found to contain T cell epitopes show homology to constant regions of the meningococcal class 3 OMP and the gonococcal porins PIA and PIB . Peptide-specific T cell lines and T cell clones were established to investigate peptide recognition in more detail . The use of a panel of HLA-typed APC revealed clear HLA-DR restriction patterns . It seems possible now to develop a (semi-) synthetic meningococcal vaccine with a limited number of constant T cell epitopes that cover all HLA-DR locus products. Hosp Pract (Off Ed), 1991 Sep, 26 Suppl 5, 14 - 9; discussion 54-5 Ceftriaxone in treatment of serious infections . Meningitis; Scheld WM; In many pediatric infectious disease programs, ceftriaxone or cefotaxime is now the preferred drug for bacterial meningitis caused by H . influenzae, meningococci, and pneumococci . Ceftriaxone reaches a high bactericidal titer in the cerebrospinal fluid and persists at the site of infection longer than any other beta-lactam antibiotic . Short-course, once-daily therapy with ceftriaxone requires more study; currently, many pediatricians administer the agent twice daily for suspected or proven meningitis . Given the association of sequelae with prolongation of positive CSF cultures, ceftriaxone's rapid bactericidal activity is an advantage, which may require an adjunctive agent to block the inflammatory response due to antibiotic-induced release of endotoxin and other cell wall components . As empiric therapy, ceftriaxone is effective in infants and children three months to 18 years old . It is not yet recommended in neonates, because of concerns about bilirubin displacement . Thus, infants up to three months of age should receive ampicillin plus cefotaxime . In adults, ceftriaxone is effective therapy for presumed bacterial meningitis but must be combined with ampicillin initially, since L . monocytogenes meningitis cannot be excluded in most cases until CSF culture results are available. J Infect Dis, 1991 Sep, 164(3), 542 - 9 Effect of polymyxin B on experimental shock from meningococcal and Escherichia coli endotoxins; Baldwin G et al.; Meningococcemia is the most frequent cause of septic shock in healthy children . To determine whether polymyxin B (PMB) might improve mortality from meningococcal shock, its protective activity was evaluated in rabbits challenged with an LD90 of meningococcal lipooligosaccharide (LOS) and compared with an LD80 of Escherichia coli O111:B4 lipopolysaccharide (LPS) . PMB (5 mg/kg) administered intravenously 30 min before meningococcal LOS challenge had no significant effect on heart rate, mean arterial pressure, serum bicarbonate, serum tumor necrosis factor (TNF) levels, or survival relative to controls . However, PMB premixed with LOS in vitro increased serum bicarbonate levels (P less than .05) and improved 24-h survival (P less than .05) . In contrast, PMB given before E . coli LPS challenge increased serum bicarbonate levels, decreased TNF levels, and improved 24-h survival (all, P less than .05) . In vitro studies confirmed that PMB at 10 micrograms/ml neutralized E . coli LPS but not meningococcal LOS activity . Thus, pretreatment with PMB apparently protects rabbits against shock induced by E . coli LPS but not by meningococcal LOS. Zh Mikrobiol Epidemiol Immunobiol, 1991 Sep, (9), 35 - 7 {The determination of antimeningococcal antibodies in the saliva of healthy people}; Martynov IuV et al.; The determination of antibodies to the group-specific polysaccharide of group A meningococci (PS-A) in the saliva of 162 healthy persons at different seasons of the year revealed that antimeningococcal antibodies could be detected in all examines . The range of concentrations of antibodies to PS-A varied between 0.1 and 33.0 U/ml . The comparison of antibody content with the levels of morbidity in meningococcal infection and carriership made it possible to determine two threshold levels of antibody concentration: 9.0 U/ml and 18.0 U/ml. J Infect, 1991 Sep, 23(2), 155 - 9 Meningococcal infection: evidence for school transmission; Wall R et al.; Intimate contacts of a patient with meningococcal disease are at greater risk of disease than the general population and are offered chemoprophylaxis in order to prevent secondary cases . School contact is not considered a risk factor unless a further case develops . Bacteriological sampling of contacts to identify potential sources of infection is not considered warranted . We have questioned these approaches and investigated the contacts of a 9-year-old child with meningitis caused by sulphonamide-sensitive Neisseria meningitidis group C . Household carriers were not identified but 7/34 classmates were carrying the index strain suggesting that transmission was occurring within this population . The current recommendations for prophylaxis are based on information gathered in socioepidemiological settings, and involving strains which differ from those now prevalent . Such extrapolations may not be justified and further microbiological studies seem warranted to re-examine meningococcal transmission and prophylaxis usage in school children. Infect Immun, 1991 Sep, 59(9), 3169 - 75 Evidence for functionally distinct pili expressed by Neisseria meningitidis; Pinner RW et al.; In order to investigate possible functional consequences of phase and antigenic variation of meningococci, the attachment of 15 strains of Neisseria meningitidis to human erythrocytes was studied by a nitrocellulose hemadsorption assay . This assay allows the study of individual meningococcal colonies with respect to erythrocyte attachment . Of the 15 strains studied, 7 demonstrated binding of human erythrocytes (HA+) . Among these seven strains, the percentage of colonies that were HA+ ranged from 0.2 to 97% . Meningococcal colonies that did not produce pilin (the major structural subunit of pili) did not demonstrate erythrocyte binding (HA-) . The HA+ colony phenotype was correlated with assembly of pilin into pili and expression of pili on the meningococcal surface . However, only some piliated colonies bound human erythrocytes . This could not be explained by differences between piliated HA+ and HA- colonies in the amount of pilin produced or by differences in number of pili expressed per diplococcus . Pili of five of the meningococcal strains with HA+ colonies were antigenically related to gonococcal pili (class I meningococcal pili), but HA+ colonies were also seen in two meningococcal strains expressing class II meningococcal pili . Changes from HA+ to HA- and from HA- to HA+, in the presence of continuing pilin production and pilus assembly, occurred at frequencies of up to 10(-2)/CFU per generation . Such frequencies resemble those of phase and antigenic variation described previously for Neisseria species pilin . These studies indicate that phase variation influences the ability of meningococci to attach to human cells and suggest that meningococci may express functionally different pili. Infect Immun, 1991 Sep, 59(9), 2963 - 71 Topology of outer membrane porins in pathogenic Neisseria spp; van der Ley P et al.; In Escherichia coli, membrane-spanning amphipathic beta-sheet structures are characteristic of many outer membrane proteins . By applying the principles that have been recognized for them to the four classes of neisserial porins, we have constructed a model for the topology of the porins within the outer membrane . This model predicts eight surface-exposed loops, both in the meningococcal class 1 and 2 proteins and in the gonococcal PIA and PIB proteins . The transmembrane sequences are highly conserved among these porins and are able to form an amphipathic beta-sheet structure . The surface-exposed hydrophilic loops show extensive variation in both length and sequence . Experimental evidence in support of this model has been obtained by using antisera against synthetic peptides which correspond to surface-exposed loops in class 1 and 2 proteins . Thus, binding to the cell surface was observed with antibodies against loops 1, 4, and 5 of class 1 and loops 1 and 5 of class 2 . In class 1, these loops are the longest ones and show the highest sequence diversity among strains of different subtypes . Mapping of epitopes recognized by monoclonal antibodies with bactericidal activity has also provided strong support for the model . The epitopes are located in loops 1 and 4 of class 1 protein, loop 5 of PIB, and loop 6 of PIA . A nonbactericidal antibody that binds only weakly to whole cells was shown to recognize loop 3 of PIB . These results suggest that the longest loops are immunodominant, provide the binding sites for bactericidal antibodies, and display the greatest variation among different strains. Lancet, 1991 Aug 31, 338(8766), 554 - 7 Influenza A and meningococcal disease; Cartwright KA et al.; There are several anecdotal accounts of the association between outbreaks of influenza and meningococcal disease . The exceptional increase in the number of cases of meningococcal infection 2 weeks after an influenza A outbreak in England and Wales during November and December, 1989, provided an opportunity to investigate the relation between the two events . Patients with meningococcal disease in December, 1989, were more likely than age-matched controls to show serological evidence of recent influenza A infection (odds ratio 3.9, 95% Cl 1.2-13.9) . The most likely explanation for the association is immune suppression induced by influenza A, though a lowering of mucosal resistance to meningococcal invasion may also be a factor . Public health authorities should be aware of the association and should be prepared to alert medical practitioners and the public to the increased risk of meningococcal disease when influenza A outbreaks occur. Proc Natl Acad Sci U S A, 1991 Aug 15, 88(16), 7175 - 9 Antibodies to poly{(2----8)-alpha-N-acetylneuraminic acid} and poly{(2----9)-alpha-N-acetylneuraminic acid} are elicited by immunization of mice with Escherichia coli K92 conjugates: potential vaccines for groups B and C meningococci and E . coli K1; Devi SJ et al.; Meningitis and other systemic infections caused by group B Neisseria meningitidis and Escherichia coli K1 remain important problems . The capsular polysaccharides (CPs) of these pathogens (poly{(2----8)-alpha-N-acetylneuraminic acid} or poly(alpha 2-8NeuNAc} are identical and are virulence factors and protective antigens for both . CP vaccines for these pathogens are not available because poly(alpha 2-8NeuNAc) alone, as a complex or a conjugate, is poorly immunogenic . Because oligomers of poly(alpha 2-8NeuNAc) in fetal brain and other tissues bind antibodies in vitro, it has been suggested that antibodies to this CP might be pathologic . We synthesized conjugates of this CP with tetanus toxoid under conditions that avoid lactone formation . Using this scheme, we also synthesized conjugates of group C meningococcal CP (poly{(2----9)-alpha-N-acetylneuraminic acid} or poly(alpha 2-9NeuNAc} and of E . coli K92 CP {poly(alpha 2-8, alpha 2-9NeuNAc)} . When injected s.c . in saline into mice, conjugates of poly(alpha 2-8NeuNAc) or poly(alpha 2-9NeuNAc) elicited homologous antibodies . E . coli K92 conjugates elicited both poly(alpha 2-8NeuNAc) and poly(alpha 2-9NeuNAc) antibodies . Both components of the conjugates expressed T-dependent immunologic properties under conditions and dosages acceptable for clinical evaluation . Poly(alpha 2-8NeuNAc) antibodies elicited by the homologous or the K92 conjugates had lower binding activities at 37 degrees C than at 22 degrees C . "Natural" poly(alpha 2-8NeuNAc) antibodies were present in almost all matched pairs of human maternal and cord sera; most cord levels were higher than in corresponding maternal sera . These findings suggest that increased levels of poly(alpha 2-8NeuNAc) IgG antibodies elicited by our conjugates will confer protective immunity to group B meningococci and E . coli K1 and will not be pathologic. Can J Microbiol, 1991 Aug, 37(8), 613 - 7 Serotypes and subtypes of Neisseria meningitidis serogroup B strains associated with meningococcal disease in Canada, 1977-1989; Ashton FE et al.; Typing of Neisseria meningitidis serogroup B disease isolates was carried out using a panel of serotype-and subtype-specific monoclonal antibodies (MAbs) in enzyme-linked immunosorbent assays (ELISA) . Three hundred and sixty-two strains isolated from 1977 to 1986 were typed using five serotyping and seven subtyping reagents and outer membrane vesicles as antigens . Serotype 2b accounted for 30% of the disease isolates . The most common subtype was P1.2, which occurred on 18.5% of all strains or 48.6% of the serotype 2b strains . Of the 362 strains typed, 135 (37.3%) were serotyped and 122 (33.7%) were subtyped . Overall, 185 (51.1%) of the strains could be assigned a serotype and (or) subtype . Strains (221) isolated during the years 1987-1989 were typed using a panel of 6 serotyping and 12 subtyping reagents by whole-cell ELISA . Strains of serotypes 4 (21.7%) and 15 (20.8%) were the most common and carried a wide variety of subtypes . The most common subtypes were P1.2 (11.8%) and P1.16 (9.5%) . Of the 221 strains analyzed, 132 (59.7%) were assigned a serotype and 123 (55.7%) a subtype and with all 18 MAbs, 192 (86.9%) of the strains were serotyped and (or) subtyped . Two different MAbs to the four epitopes 2a, 15, P1.2, and P1.16 gave discordant reactions of 0.3, 6.6, 2.6, and 2.2%, respectively, when used to analyze over 300 strains of N . meningitidis. J Immunol, 1991 Aug 1, 147(3), 915 - 20 Amino acid sequence of the FV region of a human monoclonal IgM (NOV) with specificity for the capsular polysaccharide of the group B meningococcus and of Escherichia coli K1, which cross-reacts with polynucleotides and with denatured DNA; Gawinowicz MA et al.; The complete amino acid sequences of the VH and VL regions of a biologically significant Ig, IgMNOV, were determined . IgMNOV is reactive with the capsular polysaccharide of the group B meningococcus and of Escherichia coli K1 . As reported earlier, it cross-reacts completely with polynucleotides poly(A) and poly(I) and to a lesser extent with denatured DNA and protects newborn rats against infection with E . coli K1, and is equal in potency to the standard horse anti-group B meningococcal serum . The reduced and alkylated chains were sequenced directly, identifying the L chain as lambda-subgroup II and the mu-H chain as subgroup III . The complete sequence of the VL region was determined by sequencing peptides generated by cleavage with Staphylococcus aureus protease, chymotrypsin, and trypsin . The H chain was cleaved with cyanogen bromide followed by enzymatic cleavages to obtain a large part of the VH region sequence . The structure was completed by sequencing tryptic peptides of the Fab fragment and by mass-spectrometric analysis. APMIS, 1991 Aug, 99(8), 769 - 72 Immunization against serogroup B meningococci . Opsonin response in vaccinees as measured by chemiluminescence; Lehmann AK et al.; One hundred and thirteen healthy volunteers were immunized twice (six weeks apart) with four different doses (12.5, 25, 50 and 100 micrograms, measured as protein content) of an outer membrane vesicle vaccine from a serogroup B meningococcal strain (44/76, B:15:P1.16) complexed to serogroup C meningococcal polysaccharide and/or Al(OH)3 i.e . 12 different vaccines . Serum opsonic activity against the serogroup B strain was measured using a chemiluminescence method . A significant rise in serum opsonic activity was demonstrated in 84 volunteers (74%) six weeks after the first injection and in 97 (86%) six weeks after the second . All vaccinees with low preimmunization values (less than 25 mVs) experienced a significant increase in opsonic activity . A dose-related response was most evident for the vaccines containing adjuvant, and these vaccines were associated with a maximum response six weeks after the second injection, while the vaccines without Al(OH)3 induced a peak response six weeks after the first injection . The postimmunization opsonic activity was similar to that found in convalescent sera, indicating that the vaccines may protect against serogroup B meningococcal disease. J Infect Dis, 1991 Aug, 164(2), 375 - 82 Variation in class 5 protein expression by serogroup A meningococci during a meningitis epidemic; Achtman M et al.; Serogroup A meningococci were isolated from patients and healthy carriers in The Gambia between 1982 and 1988 . The class 5 proteins expressed by these bacteria were identified by electrophoretic migration and by serologic tests . Three protein serologic groupings (seroclasses) called A (protein 5a), B (proteins 5b, 5d, or 5e), and C (protein 5c or 5C) were found among 331 bacterial isolates . The number of class 5 proteins expressed per isolate varied from none to four, with a median of two . The class 5 protein composition differed for certain paired isolates obtained from the nasopharynx, blood, and cerebrospinal fluid of diseased patients and for certain pairs of sequential isolates from the nasopharynx of healthy carriers; the medical relevance of this variation remains unclear, although the 5C protein was preferentially isolated from the nasopharynx and the 5a protein from diseased patients . The data show that a large proportion of healthy carriers in The Gambia were exposed to bacteria expressing each of the three seroclasses and that many people were exposed to bacteria expressing each of the three seroclasses and that many people were exposed to two or all three seroclasses during the epidemic of 1982-1983. J Infect Dis, 1991 Aug, 164(2), 368 - 74 Meningococcal disease in the United States--1986 . Meningococcal Disease Study Group; Pinner RW et al.; Active surveillance for invasive meningococcal disease was conducted during 1986 and 1987 in six areas of the United States with a total population of approximately 34 million persons . The incidence of meningococcal disease was 1.3:10(5) . The highest incidence of disease among the surveillance areas was in Los Angeles County (1.65:10(5) . Neisseria meningitidis serogroups B and C caused about equal amounts of disease, which reflects a recent increase in the incidence of group C disease . Group C caused more than half of the cases of meningococcal disease in Los Angeles and Tennessee but less than one-third of the cases in Missouri and Oklahoma . Multilocus enzyme electrophoresis demonstrated that a group of closely related isolates of N . meningitidis was prevalent in Los Angeles during the surveillance period and was associated with an increased incidence of meningococcal disease there. Anal Biochem, 1991 Aug 1, 196(2), 421 - 6 Preparation and application of a fluorescein-labeled peptide for determining the affinity constant of a monoclonal antibody-hapten complex by fluorescence polarization; Jiskoot W et al.; A simple and rapid method for determining the affinity constant of a monoclonal antibody-peptide complex under equilibrium conditions is presented . A peptide corresponding to sequence 178-185 of meningococcal strain MC50 class 1 outer membrane protein, which is recognized by monoclonal antibody MN12 (mouse IgG2a), was synthesized . After fluorescein was coupled to the peptide, the peptide-fluorescein conjugate was used for binding studies with MN12, employing fluorescence polarization of the fluorescein label to probe the bound fraction of the peptide . Scatchard analysis showed that the affinity constant was pH dependent . Storage of MN12 under alkaline conditions resulted in a loss of antigen-binding sites, but did not alter the affinity constant . Sips plots showed a homogeneity index of unity. Mol Microbiol, 1991 Aug, 5(8), 1831 - 41 The role of pili in the interactions of pathogenic Neisseria with cultured human endothelial cells; Virji M et al.; The influence of the two surface structures of Neisseria meningitidis, capsule and pili, in bacterial interactions with human endothelial cells was investigated . Increased association correlated with the presence of pili on bacteria while capsule type had no apparent effect . Strains expressing both Class I and Class II pili associated with endothelial cells in significantly larger numbers compared with the non-piliated variants of the same strains (greater than 10x) . Variants of Neisseria gonorrhoeae strain P9 expressing antigenically distinct pili also associated with endothelial cells in larger numbers (greater than 30x) compared with the non-piliated variant . Electron microscopic studies confirmed these data and showed that gonococci were internalized more frequently compared with meningococci . One consequence of increased association was an increase in the cytopathic effect of bacteria on the target cells. Acta Virol, 1991 Aug, 35(4), 313 - 21 The complex of flavivirus envelope polypeptide with meningococcal proteosomes elicits formation of virus-neutralizing antibodies; Slavik I et al.; Polypeptide E of tick-borne encephalitis virus was isolated in sucrose density gradient and mixed with equal weight portion of meningococcal proteosomes in the presence of N-dodecyl-N,N-dimethylglycine . Mutual complexing of viral and bacterial molecules occurred after removal of detergent by dialysis . Complexed particles appeared in the electron microscope as 40-50 microns thick short-rod structures covered on their surface with both, delicate poppy-like grains, or envelope subunit-like clustered molecules . Even when applied without adjuvant, the complex of tick-borne encephalitis virus polypeptide E with meningococcal proteosomes elicited in mice a marked antiviral as well as antibacterial humoral response. S Afr Med J, 1991 Jul 20, 80(2), 105 - 6 Deficiency of the seventh component of complement . A case report; Cooper RC et al.; Deficiency of the 7th component of the complement cascade was diagnosed in a white male with recurrent meningococcal infections . This deficiency has not previously been reported in South Africa. Zh Mikrobiol Epidemiol Immunobiol, 1991 Jul, (7), 48 - 51 {The characteristics of the serological diagnosis of meningococcal infection in children in the 1st years of life}; Martynov IuV et al.; The results of clinico-immunological examination of 181 children, aged 1 month to 6 years, with generalized forms of meningococcal infection are presented . In children under observation antimeningococcal antibodies to group-specific meningococci of the main groups A, B and C were determined over the course of the disease by passive hemagglutination (PHA) test and enzyme immunoassay (EIA) . The level and frequency of seroconversion were found to depend on the patient's age and the severity of the clinical course of meningococcal infection . Antibody level was found to increase simultaneously with respect to several meningococcal polysaccharides: A, B in 18.5% and A, B, C in 3.3% of cases . In the clinical interpretation of data obtained in the PHA test and EIA not only the patient's age, the form and duration of meningococcal infection, but also serotherapy should be taken into consideration, as the latter may distort the serological results. Zh Mikrobiol Epidemiol Immunobiol, 1991 Jul, (7), 29 - 32 {The drug sensitivity of meningococci and the characteristics of its determination}; Deviatkina NP et al.; The results obtained in the study of antibiotic and sulfamide sensitivity of 197 Neisseria meningitidis strains of groups A, B and C, isolated from the spinal fluid and blood of patients with meningococcal infection hospitalized in the 2nd Clinico-Infectious Hospital, Moscow, in 1984-1989 and studied with the use of the disc diffusion method and the method of serial dilutions of antibiotics in solid culture media, are presented . As revealed in this study, N . meningitidis strains retained their high sensitivity to penicillin and ampicillin (MIC50 = 0.016 and 0.032 micrograms/ml respectively) . Sensitivity to tetracycline decreased (MIC50 = 0.5 micrograms/ml) and to rifampicin increased (MIC50 = 0.063 micrograms/ml) . 48.5% of strains were resistant to streptomycin . In recent years the proportion of N . meningitidis, resistant to sulfanilamide preparations, significantly decreased and MIC50 was equal to 2.5 micrograms/ml in comparison with 5-10 micrograms/ml in the preceding period . The results of testing sensitivity to antibiotics by both methods coincided . Still the disc diffusion method can be used in epidemiological surveillance on meningococcal infection, while for more exact differentiation of N . meningitidis strains the use of the method of serial dilutions is necessary. Zh Mikrobiol Epidemiol Immunobiol, 1991 Jul, (7), 17 - 20 {The antilysozyme activity of meningococci}; Bukharin OV et al.; The antilysozyme activity of 184 meningococcal strains was studied . Such activity was found in all strains within the range 1-25 micrograms/ml, which was due to the heterogeneity of bacterial population . Strains varying in the total level of their lysozyme activity differed in the population structure by this sign . Preparations inhibiting antilysozyme activity could be differentiated according to the character of their action by the method of the population analysis . In the process of phagocytosis the selection of clones with a high level of antilysozyme activity was found to occur . The antilysozyme factor, heat resistant protein with a molecular weight of 10,000-30,000 D, was sensitive to trypsin. Clin Exp Rheumatol, 1991 Jul-Aug, 9(4), 411 - 2 Isolated septic meningococcal arthritis; Mader R et al.; Among the different types of arthritis associated with meningococcal disease, isolated primary meningococcal arthritis is unusual . A case of isolated group C meningococcal septic arthritis in an HIV negative homosexual male is described and its possible implication discussed. Eur J Epidemiol, 1991 Jul, 7(4), 431 - 3 Meningococcal meningitis in Italy: 1887-1986; Ballada D et al.; In Italy three epidemic peaks of meningococcal meningitis have occurred reflecting pandemic recrudescence of the disease . The seasonal distribution of the disease is similar in the epidemic or non-epidemic periods . There is no significant difference in the regional distribution of the disease . The disease is more prevalent among young males . The prevalent serogroup of Neisseria meningitidis is C . There has been a decrease in resistance to sulphonamides and an increase to rifampin among the isolated strains. J Clin Microbiol, 1991 Jul, 29(7), 1486 - 92 Characterization of serogroup A and B strains of Neisseria meningitidis with serotype 4 and 21 monoclonal antibodies and by multilocus enzyme electrophoresis; Wedege E et al.; The reactions of serogroup A strains of Neisseria meningitidis with one monoclonal antibody specific for serotype 21 and three different monoclonal antibodies specific for serotype 4 were compared with those of serogroup B strains previously assigned to serotype 4 . Antibody binding was studied by enzyme-linked immunosorbent assay (ELISA), dot blotting, and immunoblotting . Characterization of the isolates by the electrophoretic mobilities of 14 metabolic enzymes showed 50 multilocus enzyme genotypes . All except two genotypes fell into three distinct clusters: I, IIa and IIb . The enzyme genotypes of serogroup B strains were mainly in cluster I, and 88% of the serogroup A strains had genotypes in clusters IIa and IIb . Serogroup B strains generally reacted with all three serotype 4 monoclonal antibodies in ELISA and dot blotting but with only two in immunoblots . Serogroup A strains showed two different reactions in the blotting methods: either binding of the serotype 21 antibody only or binding of this and two of the three serotype 4 monoclonal antibodies . Strains of the first pattern were in clusters I and IIa, whereas all but two strains in cluster IIb were of the second pattern . In ELISA, an additional reaction of two of the serotype 4 monoclonal antibodies with serogroup A isolates was observed . The different binding of these two monoclonal antibodies in ELISA and the blotting methods appeared to result from heat inactivation of the meningococcal cells and use of detergent-containing reagents in ELISA . The results show that the serotype of serogroup A strains is distinct from serotype 4 of serogroup B strains. J Clin Microbiol, 1991 Jul, 29(7), 1447 - 52 Production of polyclonal and monoclonal antibodies against group A, B, and C capsular polysaccharides of Neisseria meningitidis and preparation of latex reagents; Nato F et al.; Polyclonal and monoclonal antibodies against capsular polysaccharides of Neisseria meningitidis serogroups A, B, and C were produced in order to develop immunological reagents allowing both the detection of soluble antigens during meningococcal meningitis and antigenic serogrouping of N . meningitidis cultures . The performance characteristics of monoclonal and polyclonal antibody latex reagents were compared . For the detection of soluble polysaccharide antigen, polyclonal antibody latex reagent was selected for N . meningitidis A and C . The latex reagent prepared with polyclonal antibodies against N . meningitidis B could not detect capsular polysaccharide even at 1 mg/ml . The monoclonal antibody B latex reagent which detected 100 ng of polysaccharide per ml was therefore chosen . For the serogroup identification of N . meningitidis, the use of a confirmatory test results in an overall specificity of 100% with polyclonal or monoclonal antibody latex reagents. J Clin Microbiol, 1991 Jul, 29(7), 1356 - 8 Monoclonal antibodies specific for the phase-variant O-acetylated K1 capsule of Escherichia coli; Torensma R et al.; Two monoclonal antibodies, one each of the immunoglobulin M and G2b types, were produced from mouse spleen cells . These monoclonal antibodies only reacted with approximately 50% of the Escherichia coli K1 strains and not against group B meningococci . No reaction was observed after the strains were boiled . E . coli K1 strains that reacted with the monoclonal antibodies could become nonreactive after subculture . Based on these findings, we conclude that the monoclonal antibodies react with the O-acetylated K1 capsule. An Esp Pediatr, 1991 Jul, 35(1), 21 - 5 {Hemodynamic study in meningococcal septic shock}; Mar Molinero F et al.; We analyzed 8 cases of meningococcal septic shock diagnosed in a three year period . The age varied from 20 months to 10 years (mean: 4.8 years) . Two patients died . Every child was monitored with a Swan-Ganz catheter 5 F or 7F, placed on by puncture of internal jugular or subclavicular veins . Of this hemodynamic study, we can conclude that in septic shock, there is a myocardial depression, that persist for several days, and improves with dopamine and dobutamine . In addition to this, in sepsis exists a pulmonary hypertension that makes worse the prognosis. Lancet, 1991 Jun 29, 337(8757), 1568 - 9 Rapid diagnosis of meningococcal meningitis by polymerase chain reaction; Kristiansen BE et al.; Rapid diagnosis of meningococcal disease followed by early treatment is essential . However, culture of blood or cerebrospinal fluid (CSF) may be unsuccessful because antibiotic treatment is often started before adequate specimens are collected, and because bacteria may die during transportation to the laboratory . We have used the polymerase chain reaction (PCR) to detect meningococcal DNA in a culture-negative CSF of a 15-year-old girl with meningococcal disease . Two oligonucleotides flanking the dihydropteroate synthase gene (dhps) of Neisseria meningitidis were used as primers . The PCR reaction is a rapid technique for the early detection of meningococcal meningitis, and also when culture is negative. Harefuah, 1991 Jun 2, 120(11), 641 - 3 {Alternating rifampicin and ceftriaxone for Neisseria meningitidis eradication in contacts}; Shehab S et al.; Following the occurrence of a case of meningococcal disease in a kibbutz, extensive preventive measures were instituted, consisting of alternate courses of rifampicin (10 mg/kg for 2 consecutive days) and ceftriaxone (single IM injection of 125 mg) . Throughout the observation period Neisseria meningitidis was absent from oropharyngeal secretions of all those treated, but was found in those of an untreated control group . The alternate use of rifampicin and ceftriaxone should be considered for the long-term prevention of the occurrence of oropharyngeal carriers of Neisseria meningitidis. Epidemiol Infect, 1991 Jun, 106(3), 445 - 57 Pharyngeal carriage of Neisseria meningitidis and Neisseria lactamica in households with infants within areas with high and low incidences of meningococcal disease; Olsen SF et al.; In a household survey in the Faroe Islands, an isolated community with hyperendemic occurrence of meningococcal disease due to serogroup B 15, 1604 persons were examined for pharyngeal carriage of Neisseria meningitidis and N . lactamica . Two areas were chosen having experienced high (HIA), and two having experienced low incidences (LIA) of disease . Living in HIA compared with LIA was associated with higher risk of N . meningitidis B 15 carriage and lower risk of N . lactamica carriage, with odds ratios of 2.7 (95% confidence interval (CI) 1.4-5.1, P = 0.003) and 0.41 (95% CI 0.31-0.53, P less than 0.0001), respectively . In HIA the risk of N . meningitidis carriage was much lower in non-carriers than carriers of N . lactamica, with an odds ratio of 0.19 (95% CI 0.08-0.47, P = 0.0003); in LIA this association (odds ratio 0.51, P = 0.05) was much weaker . Children 0-14 years had substantially higher risk of being carriers of N . meningitidis group B 15 if the mothers were so, with an odds ratio of 11 (95% CI 4-29, P less than 0.0001). NIPH Ann, 1991 Jun, 14(1), 11 - 22 Systemic meningococcal disease: the diagnosis on admission to hospital; Borchsenius F et al.; The clinical and laboratory findings in 176 patients hospitalized with suspected systemic meningococcal disease (MCd) are presented . All except nine patients were prospectively included in the MenOPP study . One hundred and fifteen patients were most likely to have meningococcal disease, of these 71 were confirmed with growth of meningococci in blood and/or cerebrospinal fluid (CSF) . The remaining sixty-one patients served as the control group . Both petechiae, reduced general condition, and reduced consciousness proved valuable in the diagnosis of MCd . Petechiae was the clinical sign best discriminating between MCd and the control group . Ecchymoses were specific for meningococcal disease . Among the laboratory tests C-reactive protein (CRP) and Thrombotest (TT) were the tests which most frequently were found to be abnormal in patients with meningococcal disease . A diagnostic score is computed by the aid of a multiple regression analysis . This score includes the variables skin hemorrhages, body pain, CSF cell count, TT, CRP and white blood cell count . For a patient hospitalized with suspected MCd a score of three or more supports the diagnosis and should indicate the need for rapid antibiotic therapy. Mol Microbiol, 1991 Jun, 5(6), 1429 - 37 Characterization of the opa (class 5) gene family of Neisseria meningitidis; Aho EL et al.; Class 5 outer membrane proteins of Neisseria meningitidis show both phase- and antigenic variation of expression . The proteins are encoded by a family of opa genes that share a conserved framework interspersed with three variable regions, designated the semivariable (SV) region and hypervariable regions 1 (HV1) and 2 (HV2) . In this study, we determined the number and DNA sequence of all of the opa genes of meningococcal strain FAM18, to assess the structural and antigenic variability in the family of proteins made by one strain . Pulsed field electrophoresis and Southern blotting showed that there are four opa genes in the FAM18 chromosome, and that they are not tightly clustered . DNA sequence analysis of the four cloned genes showed a modest degree of diversity in the SV region and more extensive differences in the HV1 and HV2 regions . There were four versions of HV1 and three versions of HV2 among the four genes . Each of the FAM18 opa loci contained a gene with a unique combination of SV, HV1, and HV2 sequences . We used lambda gt11 cloning and synthetic peptides to demonstrate that HV2 sequences completely encode the epitopes for two monoclonal antibodies specific for different class 5 proteins of FAM18. Acta Paediatr Jpn, 1991 Jun, 33(3), 352 - 6 An epidemic of meningococcal disease in Karachi (Pakistan): a study of children; Dure-Samin A et al.; A prospective study of 112 cases of epidemic meningococcal infection in the paediatric population is presented . The natural course of the disease, its complications, prognostic factors and therapeutic agents were studied . The cases were graded according to fixed criteria of severity which correlated well with the outcome of the disease . The gram-stain of the CSF was a sensitive and a quick method of diagnosis and crystalline penicillin a cost-effective therapy giving a good response within 48 hours in 90% of the cases. Dtsch Med Wochenschr, 1991 May 17, 116(20), 772 - 4 {Therapy-refractory fulminant meningococcal sepsis}; Eigentler A et al.; Two cases of the severe form of meningococcal infection are described . A 17-year-old girl and a (unrelated) 2-year-old boy suddenly developed fever and rigor . Several hours later petechiae of the skin were noted: they rapidly spread . On admission the girl was found to have a severe consumptive coagulopathy (prothrombin 24%, partial thromboplastin time 104 sec, fibrinogen 73 mg/dl, platelets 35,000/microliters) . She died two-and-a-half hours after admission of treatment-resistant shock . The boy had at first only a low prothrombin value (39%), but later the other coagulation values also became abnormal . He died 16 hours after admission from the consumptive coagulopathy and profound anaemia (haemoglobin 7.4 g/dl, haematocrit 0.23) . Neither patient had any clinical signs of meningitis . Isolation of Neisseria meningitidis from blood cultures confirmed the diagnosis. J Infect, 1991 May, 22(3), 273 - 6 Selective C7 complement deficiency causing recurrent meningococcal infection; McBride SJ et al.; We report on two sisters both with complete absence of the 7th component of complement . This congenital immunodeficiency disorder is associated with recurrent bacterial infection, especially that due to Neisseria species . These cases illustrate many of the well-recognised features of this disorder, but in one patient the illness was complicated by infective endocarditis due to N . meningitidis, a feature not previously reported. J Infect, 1991 May, 22(3), 259 - 61 Association of myocarditis and acute renal failure complicating meningococcal septicaemia; DaCosta DF et al.; We report a case of meningococcal septicaemia complicated by myocarditis, cardiogenic shock and acute renal failure . Following protracted haemodynamic support and haemodialysis, there was complete recovery of cardiac and renal function. Arch Intern Med, 1991 May, 151(5), 1005 - 9 A cluster of meningococcal disease on a school bus following epidemic influenza; Harrison LH et al.; An outbreak of meningococcal disease among children on a school bus offered the opportunity to study a proposed association between this infection and preceding influenza infection . Five students who rode the bus became ill with invasive group C meningococcus . Transmission was limited to the bus; there was no evidence for school transmission . All five students reported influenza-like symptoms within several weeks before the development of meningococcal disease . School absenteeism, principally due to upper respiratory tract illness, was higher during the 3 weeks before the outbreak of meningococcal disease than during any period in the preceding 3 1/2 years, suggesting an unusually severe outbreak of respiratory illness . A case-control study comparing students with and without influenza symptoms revealed that the outbreak of respiratory disease was due to B/Ann Arbor/1/86 influenza (geometric mean titers, 86 for 80 patients and 33 for 47 controls {P = .0007}) . These data add to the evidence suggesting that influenza respiratory infection predisposes to meningococcal disease. Ir J Med Sci, 1991 May, 160(5), 134 - 6 A change in meningococcal serogroups in the west of Ireland? Corbett-Feeney G. Admission of patients to University College Hospital, Galway over a five month period commencing December 1989 indicates an increase in the incidence of Neisseria Meningitidis Serogroup C . Seven cases of Group CN . Meningitidis have been identified, five of them occurring over a four week period . A review of Meningococcal isolates occurring at this hospital over eleven years since 1979 shows, serogroup B as the predominant serogroup . Thirty-six isolates identified by serogrouping shows the distribution of serogroups as follows: Serogroup B 69.4%, Serogroup C 19.4%, Serogroup A 8.3%, Serogroup Z 2.7% . Serogrouping, and when available, further serotyping of meningococcal isolates is very important in order to follow epidemiological trends in the disease and to monitor the serogroups that cause outbreaks . This information can influence measures that can be taken in the prevention of spread of the disease as for example the use of vaccination as appropriate. Voen Med Zh, 1991 May, (5), 51 - 2 {The heterogeneity of formed collectives in susceptibility to meningococcal adhesion}; Tatarnikov VM et al.; 4 patients with meningococcal infection and 141 meningococcal carriers were examined . The authors study heterogeneity of human population concerning susceptibility or stability of erythrocytes to adhesive influence of meningococci . In 17.4% of cases erythrocytes were highly susceptible to adhesion of meningococci, in 20.4% were stable to this influence, in 62.2% were moderately susceptible . The highest susceptibility of erythrocytes (out of statistics) was marked at the patients of Kirghiz and Tadjik nationalities . These indexes have the same statistic frequency for the persons with different blood groups (system ABO), independently of their rural or urban place of residence . The high susceptibility of erythrocytes (0.25 GAE or less) to adhesion of meningococci is three times more frequent among the persons with meningococcal infection and carriers of meningococcus . This connection may be regarded as a predisposition of the organism for the infection . Thus, the susceptibility of erythrocytes to adhesion of meningococci gives the possibility to determine the persons who need an urgent immunization at the forming collectives. Eur J Clin Microbiol Infect Dis, 1991 May, 10(5), 399 - 404 Meningococcal chest infections in a general hospital; Davies BI et al.; In the course of one calendar year (1989-1990), 46 specimens of respiratory secretions (from 44 patients) cultured in the microbiology department of a large district general hospital in The Netherlands were found to yield Neisseria meningitidis . Twenty-eight of the 46 samples yielded pure cultures of meningococci and 18 yielded other recognised respiratory pathogens as well . Only one patient had pneumonia, whereas 19 had acute respiratory infections and 18 acute purulent exacerbations of chronic bronchitis . The remaining patients, who had a variety of symptoms, all had purulent sputum . Only 8 of the 44 patients were under 40 years of age; 21 were aged more than 60 years . Serological grouping and subtyping showed a predominance of group B strains (in 24 of 44 patients) and 13 strains were non-groupable . The importance of recognising or overlooking meningococci in cultures of respiratory secretions is discussed. An Esp Pediatr, 1991 May, 34(5), 355 - 9 {Studying the levels of endotoxemia in meningococcal sepsis . Its relations to pregnancy and antibiotic treatment}; Loscertales Abril M et al.; The most frequent cause of toxic shock in our area is meningococcal sepsis . It is currently assumed that endotoxin produce by this bacteria, a lipopolysaccharide with toxic properties, is able to trigger shock and DIC by stimulating both arachidonic acid pathways, among other actions . Previous studies in our laboratory demonstrated significant differences (p +/- 0.001) in the amounts of endotoxins released in vitro by strains from patients and healthy carriers and statistically related criteria of severity with mortality in 256 patients in our center over the last 10 years . In the present study we attempted to establish whether plasma levels of endotoxin were correlated with the severity of the disease . We studied 32 patients with meningococcal sepsis, dividing the subjects into two groups: those in whom six or more criteria of severity were present, and those in whom less than six criteria were found . Blood levels of endotoxin were determined upon admission and after the administration of antibiotics (penicillin and chloramphenicol) using the limulus test with a chromogenic substrate (Coatest, Endotoxin, Kabivitrum, Sweden) . Levels of endotoxins were significantly higher in patients with more than six criteria of severity both upon admission (0.6 +/- 0.03) ng/ml) and 4 h . afterward (0.74 +/- 0.006 ng/ml) in comparison to children in whom the clinical picture was less serious (0.27 +/- 0.18 ng/ml and 0.27 +/- 0.18 ng/ml and 0.27 +/- 0.16 ng/ml7 t = 5.8 y t = 5.6 respectively . Endotoxin levels were highest in patients presenting shock, disseminated intravascular coagulation in the hypocoagulability phase and more than 8 criteria.(ABSTRACT TRUNCATED AT 250 WORDS) An Esp Pediatr, 1991 May, 34(5), 349 - 54 {Meningococcal sepsis in our area . Study of the disease severity factors and therapeutic management over a 10-year period}; Loscertales Abril M et al.; Meningococcal sepsis with cardiovascular manifestations is one of the leading causes of pediatric intensive care admission (14.85%) in our area . We carried out a two phase study over period of 10 years from 1979 to 1988, involving a retrospective analysis of clinical and analytical manifestations in order to determine a prognostic score of the severity of meningococcal infections in our area . A total of 86 cases were studies over a two year period . After establishing the prognostic score, we applied a previously assayed therapeutic protocol, based on the number of criteria of severity, in 170 children selected as having the same criteria . The factors of seriousness considered were: Appearance of the first symptoms less than 12 h . previously, appearance of petechia less than 6 h . previously, hyperthermia, shock at admission, absence of meningitis, fulminating course of purpura and convulsions, leukopenia less than or equal to 5,000 mm3, prothrombin activity less than or equal to 45%, platelets less than or equal to 75,000 mm3, fibrinogen less than or equal to 250 mgrs% and FPD greater than 40 micrograms/ml (p less than or equal to 0.01 (CHI SQUARE} . In the first phase of study, overall mortality was associated with the presence of three criteria, and was highest when more than seven criteria were present . The results indicate that mortality from meningococcal sepsis is linked to fulminating deterioration of hemodynamics and DIC.(ABSTRACT TRUNCATED AT 250 WORDS) J Bacteriol, 1991 May, 173(9), 2823 - 32 Endogenous sialylation of the lipooligosaccharides of Neisseria meningitidis; Mandrell RE et al.; Monoclonal antibodies (MAb) 3F11 and 06B4 recognize epitopes that are conserved on gonococcal lipooligosaccharides (LOS), present on some meningococcal LOS, and conserved on human erythrocytes . LOS of some group B and C prototype meningococcal LOS strains (LOS serotypes L1 to L8) treated with neuraminidase showed increased expression of the 3F11 and 06B4 MAb-defined epitopes . Neuraminidase-treated LOS separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver stained showed a shift in migration from a component with a mass of approximately 4.8 kDa to a component with a mass of between 4.5 and 4.6 kDa . The same strains grown in medium with excess CMP-N-acetylneuraminic acid had LOS that shifted in migration to a slightly higher component (mass, approximately 4.8 kDa) . Chemical analysis of the neuraminidase-digested products from one LOS indicated it contained approximately 1.5% sialic acid . Covalent linkage between sialic acid and the LOS was confirmed by analysis of de-O-acylated and dephosphorylated LOS by liquid secondary ion mass spectrometry . Three studies show that some mening