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MENINGITE e VACCINI - Bibliografia
(English)  -  Pag. 3
(nome scientifico = encefalite post-vaccinica)

Continua in: Pag. 1 - Pag. 2 -  Pag. 4 - Pag. 5 + Meningite dai Vaccini

vedi anche:
Vaccino pneumococcico
+  Siamo contro la cosiddetta "immunizzazione" vaccinale +  una delle principali cause della Meningite sono i vaccini

Italy: Ritirato vaccino Meningitec + info su Meningitec
- Encefalite post Vaccinica - creata e prodotta dai VACCINI

Associazione temporale di alcuni disturbi NeuroPsichiatrici DOPO la vaccinazione di bambini e adolescenti:
Uno studio Pilota con  casi-controllo

CDC e Conflitti di interesse - 1 + CDC e Conflitti di interesse - 2 + CDC e Conflitti di interesse - 3 + Corruzione
CDC conflitti di interesse anche per i vaccini

L’INCUBO "MENINGITE", il presunto nuovo TEST che invece “CREA” e diffonde, assieme ai VACCINI Pediatrici, l’EPIDEMIA.

Fino a ieri i DISINFORMATORI degli enti a tutela della salute, si ma di quella dei fatturati di Big Pharma, dicevano che i vaccini "proteggono dalle malattie", guardate invece cosa succede:

Clin Diagn Lab Immunol,
1998 Jul, 5(4), 479 - 85
 A modified enzyme-linked immunosorbent assay for measurement of antibody responses to meningococcal C polysaccharide that correlate with bactericidal responses; Granoff DM et al.; The standardized enzyme-linked immunosorbent assay (ELISA) for measurement of serum immunoglobulin G (IgG) antibody responses to meningococcal C polysaccharide has been modified to employ assay conditions that ensure specificity and favor detection primarily of high-avidity antibodies . The modified and standard assays were used to measure IgG antibody concentrations in sera of toddlers vaccinated with meningococcal polysaccharide vaccine or a meningococcal C conjugate vaccine . The results were compared to the respective complement-mediated bactericidal antibody titers . In sera obtained after one or two doses of vaccine, the correlation coefficients, r, for the results of the standard assay and bactericidal antibody titers were 0.45 and 0.29, compared to 0.85 and 0.87, respectively, for the modified assay . With the standard assay, there were no significant differences between the geometric mean antibody responses of the two vaccine groups . In contrast, with the modified assay, 5- to 20-fold higher postvaccination antibody concentrations were measured in the conjugate than in the polysaccharide group . Importantly, the results of the modified assay, but not the standard ELISA, paralleled the respective geometric mean bactericidal antibody titers . Thus, by employing conditions that favor detection of higher-avidity IgG antibody, the modified ELISA provides results that correlate closely with measurements of antibody functional activity that are thought to be important in protection against meningococcal disease.
 J Leukoc Biol, 1998 Jul, 64(1), 14 - 8
 The bactericidal/permeability-increasing protein (BPI) in antibacterial host defense; Elsbach P; The bactericidal/permeability-increasing protein (BPI) is a 456-residue cationic protein produced only by precursors of polymorphonuclear leukocytes (PMN) and is stored in the primary granules of these cells . The potent (nM) cytotoxicity of BPI is limited to gram-negative bacteria (GNB), reflecting the high affinity (<10 nM) of BPI for bacterial lipopolysaccharides (LPS) . The biological effects of isolated BPI are linked to complex formation with LPS . Binding of BPI to live bacteria via LPS causes immediate growth arrest . Actual killing coincides with later damage to the inner membrane . Complex formation of BPI with cell-associated or cell-free LPS inhibits all LPS-induced host cell responses . BPI-blocking antibodies abolish the potent activity of whole PMN lysates and inflammatory fluids against BPI-sensitive GNB . The antibacterial and the anti-endotoxin activities of BPI are fully expressed by the amino terminal half of the molecule . These properties of BPI have prompted preclinical and subsequent clinical testing of recombinant amino-terminal fragments of BPI . In animals, human BPI protein products protect against lethal injections of isolated LPS and inocula of GNB . Phase I trials in healthy human volunteers and multiple Phase I/II clinical trials have been completed or are in progress (severe pediatric meningococcemia, hemorrhagic trauma, partial hepatectomy, severe peritoneal infections, and cystic fibrosis) and two phase III trials (meningococcemia and hemorrhagic trauma) have been initiated . In none of >900 normal and severely ill individuals have issues of safety or immunogenicity been encountered . Preliminary evidence points to overall benefit in BPI-treated patients . These results suggest that BPI may have a place in the treatment of life-threatening infections and conditions associated with bacteremia and endotoxemia.
 Biotechnol Appl Biochem, 1998 Jun, 27 ( Pt 3), 189 - 96
 Expression in Escherichia coli of the lpdA gene, protein sequence analysis and immunological characterization of the P64k protein from Neisseria meningitidis; Guillen G et al.; By making use of recombinant DNA technology it is possible to characterize meningococcal outer membrane proteins (OMPs) capable of stimulating a host immune response . The lpdA gene, which codes for an OMP (P64k) from Neisseria meningitidis, was cloned in Escherichia coli . The recombinant protein was recognized by sera from patients convalescing from meningococcal disease . The monoclonal antibodies obtained against the recombinant protein recognized the natural protein on a Western blot, and monoclonal antibody 114 was assayed in ELISA with a panel of 85 N . meningitidis strains . The protein was recognized in 81 strains (95.3%); the strains that were not recognized were neither epidemic nor isolated from systemic disease . The complete amino acid sequence of P64k was obtained by automatic sequencing and MS.
 Arq Bras Cardiol, 1998 Feb, 70(2), 115 - 8
 {Meningococcemia complicated by myocarditis}; Albanesi Filho FM et al.; We report a case of a 26-year old man with meningococcemia complicated with myocarditis (ventricular dysfunction and myocardial ischemia), that required treatment for heart failure . Regression of myocardial dysfunction was observed six months after the infection.
 Pediatr Dermatol, 1998 May-Jun, 15(3), 169 - 83
 Acute infectious purpura fulminans: pathogenesis and medical management; Darmstadt GL; Purpura fulminans (PF) is a potentially disabling and life-threatening disorder characterized by acute onset of progressive cutaneous hemorrhage and necrosis, and disseminated intravascular necrosis . Acute infectious PF occurs most commonly in the setting of meningococcemia due to elaboration of endotoxin . Presence of purpura, particularly when generalized, is an important predictor of a poor outcome following meningococcal infection . Histopathologic hallmarks of acute infectious PF are dermal vascular thrombosis and secondary hemorrhagic necrosis, findings which are identical to those of the Shwartzman reaction . Acute infectious PF and the Shwartzman reaction have a common pathogenesis, involving a disturbance in the balance of anticoagulant and procoagulant activities of endothelial cells . This disturbance, which is triggered by endotoxin, appears to be mediated by cytokines, particularly interleukin-12, interferon-gamma, tumor necrosis factor-alpha, and interleukin-1, leading to the consumption of proteins C and S and antithrombin III . State-of-the-art therapeutic interventions based on recent advances in our understanding of the pathogenesis of acute infectious PF are discussed.
 J Infect Dis, 1998 Jul, 178(1), 266 - 9
 Disco fever: epidemic meningococcal disease in northeastern Argentina associated with disco patronage; Cookson ST et al.; Neisseria meningitidis is a leading cause of adult meningitis worldwide . From 5 to 14 August 1996, 8 cases of meningococcal disease occurred in Corrientes city (population 306,000) in northeastern Argentina . Those infected ranged in age from 15 to 45 years (median, 18.5) . To determine risk factors for infection, a case-control study was done . Infecting isolates were serogrouped and underwent phenotyping by multilocus enzyme electrophoresis (MLEE) and pulsed-field gel electrophoresis (PFGE) . Those infected were significantly more likely than those not infected to have had exposure to passive or active cigarette smoke or to have attended a particular disco . Isolates available from 6 case-patients were all serogroup C; all had identical MLEE and PFGE patterns . These data suggest that dance clubs or discos may be a focus of transmission of N . meningitidis among young people.
 Neth J Med, 1998 May, 52(5), 193 - 6
 Primary oligoarthritis in a parent of a child with meningococcal group B sepsis and meningitis; Bongers V et al.; The mother of an eight-month-old child with meningitis presented with petechiae on her trunk and lower extremities, fever, and oligoarthritis . Although pathogens were never revealed by Gram stain nor cultured from the aspirated joint fluid, the diagnosis was primary meningococcal arthritis . This diagnosis was based on the simultaneous occurrence of Neisseria meningitidis group B infection in her son and the clinical presentation.
 Bull World Health Organ, 1998, 76(2), 149 - 52
 Prognostic scores for use in African meningococcal epidemics; Ajayi-Obe EK et al.; Current WHO guidelines for the case management of meningococcal infections during epidemics in developing countries often cannot be applied, largely because of the limited health resources in such countries . Several scoring scales based on clinical and laboratory features in numerous combinations have been developed for the management of meningococcal infections in developed countries, and these have facilitated early identification of patients with fulminant disease and thus early intervention and reduction in mortality . Unfortunately such scoring scales are not appropriate for use in developing countries . We identified hypotension, tachycardia, tachypnoea, delay in capillary refill time, coma, absence of neck stiffness and petechiae and/or purpura as simple prognostic factors of meningococcal disease . Two scores were developed: score I, which includes all seven prognostic factors, had a sensitivity and specificity of 80% and 94%, respectively . Score II, which excluded hypotension, had a sensitivity and specificity of 73.3% and 89.7%, respectively . Quick and simple scoring scales are therefore not only applicable but useful for the case management of patients in meningococcal epidemics in developing countries.
 Aust Fam Physician, 1998 Jun, 27(6), 495 - 7
 Meningococcal disease . Is early diagnosis possible?
 Charlton R.
 Meningococcal disease is a public health problem because of its high mortality and is one disease that many GPs have not seen . Case reports illustrate that presentation is rarely classic 'meningitis' and further research is required to enable earlier detection.
 Pathology, 1998 May, 30(2), 188 - 91
 Detection of decreased penicillin susceptibility in viridans group streptococci; Pottumarthy S et al.; One hundred consecutive clinically significant viridans group streptococcal isolates had their susceptibility to penicillin determined by the penicillin E-test method . The ability of penicillin 2 and 10 unit disks and the oxacillin 1 microg disk to detect reduced penicillin susceptibility, ie; MIC > or = 0.25 microg/ml, in viridans group streptococci was determined by comparing the zone diameters against the penicillin E-test MICs . The sensitivity, specificity and predictive values of previous, existing and proposed interpretative criteria to detect decreased penicillin susceptibility were determined . Thirty-seven per cent of the isolates had reduced susceptibility to penicillin . The previous 1993 NCCLS interpretative criteria for the penicillin 10 unit disk, ie; resistant < or = 27 mm failed to detect 16 of 37 (43%) isolates with reduced penicillin susceptibility . The 1 microg oxacillin disk using existing meningococcal interpretative criteria, ie; resistant < or = 10 mm, failed to detect 11 of 37 (40%) isolates with reduced penicillin susceptibility . When the oxacillin 1 microg disk pneumococcal interpretative criteria were used, ie; resistant < or = 19 mm, all the isolates with reduced penicillin susceptibility were detected but 42 of 63 (67%) susceptible isolates were misclassified as resistant . Based on our data, we set new interpretative criteria to detect all isolates with decreased penicillin susceptibility for each of the three disks . Using our proposed zone diameters to detect decreased penicillin susceptibility of < or = 27 mm for the penicillin 2 unit disk, < or = 35 mm for the penicillin 10 unit disk, and < or = 17 mm for the oxacillin disk, 34 (54%), 44 (70%),and 21 (33%) of the 63 susceptible isolates, respectively, were misclassified as having decreased penicillin susceptibility . Our data show that the oxacillin 1 microg disk is able to detect decreased susceptibility to penicillin in viridans group streptococci with greater specificity than either penicillin 2 or 10 unit disks.
 Infect Immun, 1998 Jul, 66(7), 3223 - 31
 Immune responses against major outer membrane antigens of Neisseria meningitidis in vaccinees and controls who contracted meningococcal disease during the Norwegian serogroup B protection trial; Wedege E et al.; Sera from vaccinees and controls who contracted serogroup B meningococcal disease during the blinded and open parts of a two-dose protection trial in Norway were compared for antigen-specific and bactericidal antibodies against vaccine strain 44/76 (B:15:P1.7,16) . From 16 of 20 (80%) vaccinees and 26 of 35 (74%) controls, one or more serum samples (n = 104) were collected during the acute phase (1 to 4 days), early convalescent phase (5 to 79 days), and late convalescent phase (8 to 31 months) after onset of disease . Binding of immunoglobulin G (IgG) to the major outer membrane antigens (80- and 70-kDa proteins, class 1, 3, and 5 proteins, and lipopolysaccharide {LPS}) on immunoblots was measured by digital image analysis . Specific IgG levels in vaccinees increased from acute to early convalescent phases, followed by a decline, while controls showed a small increase over time . Vaccinees had significantly higher levels than controls against class 1 and 3 porins and LPS in acute sera, against all antigens during early convalescence, and against class 1 and 3 porins in the later sera . Vaccinees who were infected with strains expressing subtype P1.7,16 proteins demonstrated a level of IgG binding to protein P1.7,16 with early-convalescent-phase sera that was fourfold higher than that of those infected with other strains . Bactericidal titers in serum against the vaccine strain were 192-fold higher for vaccinees than those for controls during early convalescence, but similarly low levels were found during late convalescence . A vaccine-induced anamnestic response of specific and functional antibody activities was thus shown, but the decrease in protection over time after vaccination indicated that two vaccine doses did not induce sufficient levels of long-term protective antibodies.
 Infect Immun, 1998 Jul, 66(7), 3218 - 22
 Immunological and molecular characterization of three variant subtype P1.14 strains of Neisseria meningitidis; Saunders NB et al.; Epidemic outbreaks of group B meningococcal disease exhibit a clonal nature consisting of a common serotype-subtype . Subtype-specific monoclonal antibodies (MAbs) directed toward two variable regions (VR1 and VR2) of the class 1 protein of Neisseria meningitidis are used in this classification scheme . A new MAb was developed to classify a nonsubtypeable (NST) strain of N . meningitidis, 7967 . This MAb bound to both the NST strain and the prototype subtype P1 . 14 strain, S3446, by dot blot analysis . However, a MAb produced to the prototype P1.14 strain did not bind to strain 7967 . Sixteen additional strains were further identified as P1.14 with the prototype MAb; of these, 15 strains bound both MAbs . Differences in the characteristics of binding of both antibodies to the three apparently diverse P1.14 strains were studied further by using outer membrane complex proteins, immobilized peptides, and soluble peptides . Deduced amino acid analysis suggested that both MAbs bind to VR2 and that single amino acid changes within VR2 (KM, NM, or KK) might explain the differences in binding characteristics . These results demonstrated that minor variations which exist within subtype variable regions may be clearly identified only by a combination of molecular and immunologic testing . The impact of subtype variation will become more evident as subtype-specific vaccines are developed and tested for efficacy.
 Pediatr Radiol, 1998 Jun, 28(6), 426 - 8
 Preamputation MR imaging in meningococcemia and comparison to conventional arteriography; Hogan MJ et al.; Meningococcemia is a life-threatening infection which produces purpura fulminans and extremity gangrene in its most severe form . In patients with gangrene, amputation is usually necessary . The amputations frequently need revision as ischemic changes in the underlying soft tissues and bone are difficult to evaluate at the time of surgery . These ischemic changes often have non-vascular distributions and progress over time . We present two patients in whom MR imaging and MR angiography were performed prior to planned amputation . These cases demonstrate the potential utility of MR imaging in this setting, and compare the MR angiographic results to conventional arteriography in one of these patients.
 Eur J Clin Microbiol Infect Dis, 1998 Feb, 17(2), 85 - 9
 Increasing incidence of meningococcal disease in Spain associated with a new variant of serogroup C; Berron S et al.; Serogroup B has been the main cause of meningococcal disease in Spain since at least 1979, but in recent years an increase in the prevalence of infection due to serogroup C meningococci has been detected . In 1996, for the first time, most cases of meningococcal disease were caused by serogroup C strains . The sero/subtype of all serogroup C meningococci received from 1993 to June 1996 was determined, and the results showed that C:2b:P1.2,5, the most common phenotype in 1995 and 1996 (63% and 65%, respectively), represented only 4.8% of strains in 1993 . The C:2b: P1.2,5 epidemic strains appear to be responsible for the high prevalence of serogroup C in Spain . One hundred fifty-one randomly selected serogroup C strains were analyzed by multilocus enzyme electrophoresis, ribotyping, and pulsed-field gel electrophoresis . Pulsed-field gel electrophoresis provided the most accurate information: more than 80% of the C:2b:P1.2,5 and C:2b:P1.2 isolates exhibited one of two very closely related profiles, while most of the C:2b:NST and C:2b:P1.5 strains had a pattern located at a genetic distance of 0.24 from those two profiles . The results show that C:2b:P1.2,5 strains represent a subclone or a genetic variant of the previously identified Spanish epidemic clone C:2b:non-subtypable strains.
 Arq Neuropsiquiatr, 1997 Sep, 55(3B), 632 - 5
 {Acute disseminated encephalomyelitis and meningococcal A and C vaccine: case report}; Py MO et al.; A 25-year-old women developed acute disseminated post-vaccinal encephalomyelitis (ADEM) following vaccination with A plus C meningococcal vaccine (Pasteur-Merieux) . Fast disappearance of symptoms and gradual resolution of MRI demyelinating lesions occurred after steroid treatment with high doses of intravenous methylprednisolone . To our knowledge, ADEM has not been previously described in association with meningococcal vaccine . Although most cases of ADEM occur following viral infections and vaccination, the syndrome has previously been related to leptospirosis and Mycoplasma pneumoniae infections . This suggests that it may also be related to exposure to polysaccharide-protein vaccines such as the Group A plus Group C meningococcal vaccine.
 Arq Neuropsiquiatr, 1997 Sep, 55(3B), 584 - 7
 {Clinical and laboratory characteristics of pyogenic meningitis in adults}; Gomes I et al.; We reviewed the charts of 176 adult patients, admitted with a diagnosis of acute bacterial meningitis, in the Hospital Couto Maia, from January 1990 to December 1992 . All the patients had community-acquired meningitis . In 120 patients we could identify the causative agent on Gram's staining and culture . The most common pathogens were N . meningitidis (56.7%) S . pneumoniae (37.5%) and E . coli (3.3%) . The overall lethality rate was 19.8% and the lethality was greater in the group with streptococcus meningitis (31.8%) . The mean age and the leukocyte in the peripheral blood were greater in the group with S . pneumoniae meningitis than in the meningococal group . Cutaneous hemorrhagic lesions was and excellent predictor meningococcal meningitis.
 FEMS Microbiol Lett, 1998 May 15, 162(2), 215 - 8
 False positive diagnosis of meningococcal infection by the IS1106 PCR ELISA; Borrow R et al.; At a time when optimal case ascertainment for meningococcal infection is a high priority, the need for non-culture case confirmation, in particular by DNA amplification, is seen as being of vital importance to assist contact management and cluster recognition . A solution hybridisation assay with colorimetric microtitre plate detection (polymerase chain reaction-enzyme-linked immunosorbent assay (PCR ELISA) inverted question mark has been developed using the multicopy insertion sequence IS1106 which had reportedly achieved a specificity of 100% and was described as being meningococcal specific . This PCR ELISA assay was evaluated on specimens from over 5000 patients at the national Meningococcal Reference Unit (MRU) between late 1995 and early 1997 and was found to be highly sensitive . Insertion sequences, however, are genetically mobile with the ability to spread between species and even genera . During the evaluation period of the IS1106 PCR ELISA a number of false positives proved to be caused by organisms other than N . meningitidis were recorded resulting in the withdrawal of this assay as a front line screening assay for routine confirmation of meningococcal infection.
 Ann Trop Med Parasitol, 1997 Oct, 91(7), 777 - 85
 Meningococcal disease in Africa; Hart CA et al.; Neisseria meningitidis (the meningococcus) is responsible for endemic and meningococcal disease in Africa . Meningococci are placed into 12 serogroups based on their capsular polysaccharide antigens . Group-B meningococci are responsible for sporadic endemic disease . In the meningitis belt of sub-Saharan Africa, the large spreading epidemics which occur every 5-10 years are usually caused by group-A meningococci, with attack rates of 400-500/100,000 population . In the last epidemic, infection spread from the original meningitis belt to Kenya, Uganda, Rwanda, Zambia and Tanzania . Most cases of meningococcal disease are of meningitis and meningococcal septicaemia is a rare presentation except in South Africa . It is important to exclude meningococcal septicaemia since this carries the highest mortality (up to 75%) . Treatment involves intravenous chloramphenicol (or intramuscular, oily chloramphenicol), a drug which is preferable to penicillin because penicillin-resistant meningococci have already emerged in Africa . Dexamethasone treatment of meningococcal meningitis is unproven and may even be deleterious in developing countries . Prevention of epidemic meningococcal disease could be achieved by mass vaccination with protein-conjugate, group-A and -C polysaccharides, but these new vaccines are likely to be expensive.
 Clin Infect Dis, 1998 Apr, 26(4), 918 - 23
 Plasma patterns of tumor necrosis factor-alpha (TNF) and TNF soluble receptors during acute meningococcal infections and the effect of plasma exchange; van Deuren M et al.; In 39 patients with acute meningococcal infections, the plasma concentrations of tumor necrosis factor-alpha (TNF) and its soluble receptors (sRs) TNFsR-p55 and TNFsR-p75 were measured from admission till recovery . At admission, patients with shock had significantly higher TNF, TNFsR-p55, and TNFsR-p75 values than patients without shock . In addition, during the first 24 hours, patients with shock had higher TNFsR-p75 to TNFsR-p55 ratios, indicating that in shock the increase of TNFsR-p75 exceeds that of TNFsR-p55 . TNF measured more than 12 hours after admission failed to differentiate between shock and nonshock because TNF concentrations normalized within 12-24 hours . However, because concentrations of TNFsRs remained elevated for 5-6 days, at that time plasma TNFsRs still differentiated between shock and nonshock . Plasma exchange or whole blood exchange (PEBE), performed in 20 patients with shock, accelerated the decrease of plasma TNFsRs . However, because of a rebound after each PEBE session, the overall half-lives of both TNFsRs were not affected by PEBE.
 Int J Infect Dis, 1998 Jan-Mar, 2(3), 137 - 42
 Meningococcal meningitis among Rwandan refugees: diagnosis, management, and outcome in a field hospital; Heyman SN et al.; OBJECTIVE: To study the diagnostic process, clinical course, and outcome of Rwandan refugees with meningococcal meningitis, treated in an Israeli field hospital in Goma, Zaire, in the summer of 1994 . METHODS: Patient hospital charts and laboratory records were reviewed with critical evaluation of clinical presentation and diagnostic tests . Patients were treated as part of a disaster relief effort in a refugee camp experiencing several coexisting lethal epidemics . RESULTS: A total of 65 patients were identified as having group A meningococcal meningitis . Latex agglutination test for Neisseria meningitidis soluble antigen in the cerebrospinal fluid was found to be a superior diagnostic tool, as compared to Gram stain, and at least as effective as culture . The mortality rate was 14%; mortality was markedly affected by co-morbidity (e.g., dysentery, pneumonia, and malnutrition) . CONCLUSIONS: The outcome of patients with meningococcal meningitis, treated in referral centers within a disaster area may be favorable, despite overwhelming coexisting epidemics, and may be comparable to that achieved in advanced medical facilities . Encephalopathy may be a diagnostic pitfall in the perspective of coexisting epidemics, requiring a high index of suspicion and routine lumbar puncture . The latex agglutination test is highly useful in achieving prompt diagnosis of meningococcal meningitis, in particular when sample handling for culture and microscopy is suboptimal.
 J Clin Microbiol, 1998 Jun, 36(6), 1746 - 9
 Randomly amplified polymorphic DNA genotyping of serogroup A meningococci yields results similar to those obtained by multilocus enzyme electrophoresis and reveals new genotypes; Bart A et al.; Randomly amplified polymorphic DNA (RAPD) genotyping was applied to one representative strain of each of the 84 electrophoretic types (ETs) of Neisseria meningitidis serogroup A previously defined by multilocus enzyme electrophoresis (MEE) (J.-F . Wang et al., Infect . Immun . 60:5267-5282, 1992) . Twenty-seven additional isolates comprising six ETs were also tested . MEE and RAPD genotyping yielded similar dendrograms at the subgroup level . Similar results were obtained by both methods for 18 serogroup A meningococci isolated in The Netherlands between 1989 and 1993 . Ten of these isolates defined a new subgroup, designated subgroup IX . One isolate belonged to the ET-5 complex, normally associated with serogroup B strains (D . A . Caugant et al., Proc . Natl . Acad . Sci . USA 83:4927-4931, 1986) . By RAPD genotyping, meningococci can be linked to previously characterized genotypes by using a computerized database, and dendrograms based on cluster analyses can easily be generated . RAPD analysis offers advantages over MEE since intermediate numbers of isolates of serogroup A meningococci can quickly be assigned to known subgroups and new subgroups can be defined.
 Drugs, 1998 Jun, 55(6), 767 - 77
 Current drug treatment strategies for disseminated intravascular coagulation; de Jonge E et al.; Disseminated intravascular coagulation (DIC) can be caused by a variety of diseases . Experimental models of DIC have provided substantial insight into the pathogenesis of this disorder, which may ultimately result in improved treatment . Disseminated coagulation is the result of a complex imbalance of coagulation and fibrinolysis . Simultaneously occurring tissue factor-dependent activation of coagulation, depression of natural anticoagulant pathways and shutdown of endogenous fibrinolysis all contribute to the clinical picture of widespread thrombotic deposition in the microvasculature and subsequent multiple organ failure . Cornerstone for the treatment of DIC is the optimal management of the underlying disorder . At present, specific treatment of the coagulation disorders themselves is not based on firm evidence from controlled clinical trials . Plasma and platelet transfusion are used in patients with bleeding or at risk for bleeding and low levels of coagulation factors or thrombocytopenia . The role of heparin and low molecular weight heparin is controversial, but their use may be justified in patients with active DIC and clinical signs of extensive fibrin deposition such as those with meningococcal sepsis . There is some evidence to indicate that low molecular weight heparin is as effective as unfractionated heparin but may be associated with a decreased bleeding risk . Antithrombin III (AT III) replacement appears to be effective in decreasing the signs of DIC if high doses are administered, but effects on survival or other clinically significant parameters are at best uncertain . If AT III supplementation is used, the dosage should be selected to achieve normal or supranormal plasma levels of 100% or higher . Results of studies on protein C concentrate, thrombomodulin or inhibitors of tissue factor are promising, but the efficacy and safety of these novel strategies remains to be established in appropriate clinical trials.
 Glycobiology, 1998 Apr, 8(4), 359 - 65
 Characterization of terminal NeuNAcalpha2-3Galbeta1-4GlcNAc sequence in lipooligosaccharides of Neisseria meningitidis; Tsai CM et al.; Group B and C Neisseria meningitidis are the major cause of meningococcal disease in the United States and in Europe . N . meningitidis lipooligosaccharide (LOS), a major surface antigen, can be divided into 12 immunotypes of which L1 through L8 were found among Group B and C organisms . Groups B and C but not Group A may sialylate their LOSs with N-acetylneuraminic acid (NeuNAc) at the nonreducing end because they synthesize CMP-NeuNAc . Using sialic acid-galactose binding lectins as probes in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4, L5, L7, and L8) in Groups B and C bound specifically to Maackia amurensis leukoagglutinin (MAL), which recognizes NeuNAcalpha2-3Galbeta1-4GlcNAc/Glc sequence, but not to Sambucus nigra agglutinin, which binds NeuNAcalpha2-6Gal sequence . The combination of SDS-PAGE and MAL-blot analyses revealed that these six LOSs contained only the NeuNAcalpha2-3Galbeta1-4GlcNAc trisaccharide sequence in their 4.1 kDa LOS components, which have a common terminal lacto-N-neotetraose (LNnT, Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) structure when nonsialylated as shown by previous studies . The LOS-lectin binding was abolished when the LOSs were treated with Newcastle disease viral neuraminidase which cleaves alpha2-->3 linked sialic acid . Methylation analysis of a representative LOS (L2) confirmed that NeuNAc is 2-->3 linked to Gal . Thus, these LOSs structurally mimic certain glycolipids, i.e., paragloboside (LNnT-ceramide) and sialylparagloboside and some glycoproteins in having LNnT and N-acetyllactosamine sequences, respectively, with or without alpha2-->3 linked NeuNAc . The molecular mimicry of the LOSs may play a role in the pathogenesis of N.meningitidis by assisting the organism to evade host immune defenses in man.
 J Infect Dis, 1998 Jun, 177(6), 1754 - 7
 Serogroup B, electrophoretic type 15 Neisseria meningitidis in Canada; Kertesz DA et al.; Invasive meningococcal disease is nationally reportable in Canada . In recent years, a serogroup C genotype, designated electrophoretic type 15 (ET15), has been the most frequently isolated meningococcal genotype in Canada and has caused epidemics across the country . Between August 1993 and September 1995, there were 9 cases of invasive meningococcal disease caused by a variant of this genotype, expressing group B capsular polysaccharide . The appearance of serogroup B:ET15 was related temporally and geographically to mass immunization campaigns designed to control serogroup C meningococcal disease in Canada . Since there is no vaccine available to control serogroup B meningococcal disease, the appearance of this variant may have public-health significance if it demonstrates the same epidemic potential as its serogroup C counterpart.
 J Infect Dis, 1998 Jun, 177(6), 1614 - 21
 Avidity of IgG for Streptococcus pneumoniae type 6B and 23F polysaccharides in infants primed with pneumococcal conjugates and boosted with polysaccharide or conjugate vaccines; Anttila M et al.; Relative avidity of IgG to Streptococcus pneumoniae type 6B and 23F polysaccharides (PSs) was measured in sera of children immunized with pneumococcal vaccines, using an EIA and the chaotropic agent thiocyanate . Infants were immunized at 2, 4, and 6 months of age with pneumococcal PS-diphtheria toxoid conjugate vaccine, and boosted at 14 months with the homologous conjugate or a pneumococcal PS vaccine . The concentrations of antibodies to 6B and 23F PSs increased significantly after the booster with both vaccines . A significant increase in the avidity of anti-6B and anti-23F antibodies was seen after the booster with conjugate but not with PS vaccine . Avidity also increased in another group of infants primed and boosted with pneumococcal PS-meningococcal protein conjugate but not in a group boosted with PS vaccine after priming with pneumococcal PS-tetanus toxoid conjugate . In the latter group, however, the avidity of anti-6B was high before boosting.
 Clin Diagn Lab Immunol, 1998 May, 5(3), 348 - 54
 Correlation between serological and sequencing analyses of the PorB outer membrane protein in the Neisseria meningitidis serotyping system; Sacchi CT et al.; The current serological typing scheme for Neisseria meningitidis is not comprehensive; a proportion of isolates are not serotypeable . DNA sequence analysis and predicted amino acid sequences were used to characterize the structures of variable-region (VR) epitopes on N . meningitidis PorB proteins (PorB VR typing) . Twenty-six porB gene sequences were obtained from GenBank and aligned with 41 new sequences . Primary amino acid structures predicted from those genes were grouped into 30 VR families of related variants that displayed at least 60% similarity . We correlated VR families with monoclonal antibody (MAb) reactivities, establishing a relationship between VR families and epitope locations for 15 serotype-defining MAbs . The current panel of serotype-defining MAbs underestimates by at least 50% the PorB VR variability because reagents for several major VR families are lacking or because a number of VR variants within some families are not recognized by serotype-defining MAbs . These difficulties, also reported for serosubtyping based on the PorA protein, are shown as inconsistent results between serological and sequence analyses, leading to inaccurate strain identification and incomplete epidemiological data . The information from this study enabled the expansion of the panel of MAbs currently available for serotyping, by including MAbs of previously undetermined specificities . Use of the expanded serotype panel enabled us to improve the sensitivity of serotyping by resolving a number of formerly nonserotypeable strains . In most cases, this information can be used to predict the VR family placement of unknown PorB proteins without sequencing the entire porB gene . PorB VR typing complements serotyping, and a combination of both techniques may be used for full characterization of meningococcal strains . The present work represents the most complete and integrated data set of PorB VR sequences and MAb reactivities of serogroup B and C meningococci produced to date.
 Infect Immun, 1998 Jun, 66(6), 3017 - 23
 Identification and molecular analysis of lbpBA, which encodes the two-component meningococcal lactoferrin receptor; Lewis LA et al.; We identified lbpB, encoding the lipoprotein component of the meningococcal lactoferrin receptor . An LbpB mutant was unable to acquire Fe from lactoferrin and exhibits decreased surface binding to lactoferrin . Primer extension and reverse transcription-PCR analysis indicate that lbpB and lbpA are cotranscribed on a polycistronic Fe-repressible mRNA.
 Scand J Immunol, 1998 Apr, 47(4), 388 - 96
 Opsonophagocytic and bactericidal activity mediated by purified IgG subclass antibodies after vaccination with the Norwegian group B meningococcal vaccine; Aase A et al.; To study how the different immunoglobulin (Ig)G subclass antibodies may confer protection against systemic meningococcal disease, we isolated IgG1, IgG2 and IgG3 antibodies from plasma from vaccinees immunized with the Norwegian meningococcal outer membrane vesicle vaccine . Four IgG1, one IgG2 and four IgG3 preparations were purified . The IgG2 and IgG3 subclass preparations were free from contaminating subclasses, whereas the IgG1 preparations contained from 0 to 14% of IgG2 and/or IgG3 . Immunoblotting against whole-cell meningococcal antigens showed broad specificities of the various preparations, both within and between subclasses . These subclass preparations were tested for opsonophagocytic and bactericidal activity . As targets we used two different variants of the meningococcal vaccine strain, with low (44/76-SL) and high (44/76-1) expression of the outer membrane protein Opc . Using polymorphonuclear leucocytes as effector cells in the presence of human complement, all three IgG subclass preparations revealed high, and similar, opsonophagocytic activities against 44/76-SL, whereas against 44/76-1 the IgG2 preparation showed a reduced activity and most IgG3 preparations were slightly more active than the IgG1 preparations . Regarding bactericidal activity, all the three subclasses were highly active against 44/76-SL . Against 44/76-1 the bactericidal activities were somewhat more varied: all IgG1 and three IgG3 preparations exhibited higher activities than against 44/76-SL . Due to the low concentration in the IgG2 preparations, only a weak activity was seen against 44/76-1 . One IgG3 preparation that was highly opsonophagocytic revealed no bactericidal activity against either of the two bacterial variants examined . In conclusion, we have shown that the IgG subclass effector functions differ from person to person, but that antibodies of IgG1, IgG2 and IgG3 subclasses, judged by their behaviour in the functional tests, may all contribute to protection against meningococcal disease.
 Clin Infect Dis, 1998 May, 26(5), 1159 - 64
 Complications and sequelae of meningococcal disease in Quebec, Canada, 1990-1994; Erickson L et al.; To study complications and sequelae of serogroup B and C meningococcal disease, a retrospective survey examined the outcome of all culture-proven cases reported in the province of Quebec, Canada, from January 1990 through December 1994 (serogroup B, 167 cases; serogroup C, 304 cases) . Data were collected from medical files, postal questionnaires, and telephone interviews . Age groups having the most cases were the 10-19-year age group for serogroup C and the < 1-year age group for serogroup B . Fatality rates were 7% for serogroup B and 14% for serogroup C disease . Only 3% of survivors of serogroup B disease had physical sequelae, compared with 15% of survivors of serogroup C disease (skin scars, 12%; amputations, 5%; hearing loss, 2%; renal problems, 1%; and other sequelae, 4%) . These results confirm the gravity of disease caused by serogroup C, serotype 2a Neisseria meningitidis and justify liberal use of vaccination for outbreak control.
 Croat Med J, 1998 Mar, 39(1), 62 - 5
 Familial epidemic of meningococcal disease; Smilovic V et al.; Two closely related boys from the same house hold (Home 1), aged two and three, were affected with fulminant meningococcal sepsis known as Waterhouse-Friderichsen syndrome . Neisseria meningitidis serogorup B was isolated from their blood and cerebrospinal fluid . The two-year-old boy died one day after the onset of the disease . Epidemiological examination of contacts and pharyngeal swabs were performed in 14 persons from the household, all of them relatives of the affected children, as well as in a number of other contacts . Chemoprophylaxis with cotrimoxazole was simultaneously administered to all contacts . Family histories revealed that two contacts from the household where the patients did not live (Home 2) were inadvertently omitted . Subsequent examinations, following a report of another contagious disease (salmonelosis), revealed that these two persons were Neisseria meningitidis carriers, together with another one in the same household . The carriers most probably caused the infection of a third, five-year-old boy, the deceased boy's brother (Home 1) who also developed fulminant meningococcal sepsis . The failure to take the appropriate prophylaxis led to a prolonged carrier state in the carrier from the second household . Repeated pharyngeal swab sampling revealed two more carriers from both households that had previously been negative . Control of the epidemic was achieved after 5 weeks by repeated and controlled chemoprophylaxis with ciprofloxacin, and by repeated epidemiological examinations, disinfection, and daily health surveillance by the Sanitary Inspectorate . This extremely rare instance of a familial epidemic with three infected persons emphasizes the need for consistent chemoprophylaxis in meningococcal disease contacts.
 Rev Saude Publica, 1997 Aug, 31(4), 402 - 16
 {Immunologic behavior of meningococcal vaccines}; Requejo HI; Meningococcal disease continues to be a great health problem on all continents and the meningococcal vaccines have been proposed for their prevention and epidemic control . The polysaccharide A and C vaccines are relatively efficacious with distinct immunological behavior with regard to the different age groups, however, up to the present no highly efficacious vaccine for meningococcal B disease exists . The meningococcal B capsular polysaccharide is not immunogenic due to the structural mimicry of mammalian tissues and efforts to produce carrier proteins have been proposed in order to obtain an immunogenic vaccine for all age groups that would if possible, protect against all the meningococci . This review of the literature presents the study of the development of the immunological behavior of all the meningococcal vaccines undergoing development and reports on the efforts to obtain a safe and efficacious product for the control of meningococcal disease.
 FEMS Microbiol Lett, 1998 May 1, 162(1), 25 - 30
 Identification of a human cDNA clone that mediates adherence of pathogenic Neisseria to non-binding cells; Jonsson AB; Neisseria gonorrhoeae and Neisseria meningitidis are exclusively human pathogens . A crucial property of the pathogenicity of neisserial infection is the ability to adhere to human epithelial cells . Pili mediate adherence of these bacteria to target cells and thereby promote colonization and infection of mucosal surfaces . In order to identify and to learn more about the initial event during infection, a cDNA clone from a human cervical epithelial cell line was identified in a panning experiment using purified gonococcal pili as probe . Upon transfection of the cloned cDNA into COS-7 cells, both gonococci and meningococci adhered to these otherwise non-binding cells . The deduced amino acid sequence of the cDNA clone showed homology to a recently reported human cDNA, called WWP2, that encodes an N-terminal C2-like domain . The C2 domain has been shown to bind membrane phospholipids in a calcium-dependent manner and is thought to function in the intracellular compartmentalization of proteins . Antiserum raised against the product encoded by the cDNA did not inhibit bacterial adherence, indicating that the cloned gene is most likely involved in up-regulation of a surface receptor for pathogenic Neisseria.
 J Infect Dis, 1998 May, 177(5), 1401 - 5
 Posttranscriptional down-regulation of tumor necrosis factor-alpha and interleukin-1beta production in acute meningococcal infections; van Deuren M et al.; The regulation of tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1beta) production was studied in patients with meningococcal disease . Circulating TNF and IL-1beta normalized within 1 day . TNF mRNA and IL-1beta mRNA in white blood cells decreased over 3-4 days . During the acute stage, TNF and IL-1beta production in stimulated whole blood cultures was down-regulated . After 4-5 days, this production was restored . The down-regulation was unlikely to be caused by circulating IL-6 and IL-10, as these cytokines normalized within 2-3 days . TNF mRNA in stimulated cultures during the acute stage, with down-regulated production, did not differ from that at recovery, with restored production . In contrast, the down-regulated production of IL-1beta was associated with significantly lower IL-1beta mRNA levels . Thus, TNF and IL-1beta production are differentially regulated . Whereas TNF production is regulated posttranscriptionally, IL-1beta production is also regulated at the mRNA level.
 Crit Care Med, 1998 May, 26(5), 965 - 8
 Protein C in the treatment of coagulopathy in meningococcal disease; Rintala E et al.; OBJECTIVE: To evaluate the clinical and laboratory effects of the substitution of protein C (PC) as an adjunct to conventional therapy in the treatment of purpura fulminans associated with meningococcal sepsis . DESIGN: case series . SETTING: Medical and medical-surgical intensive care units of two university hospitals . PATIENTS: Three patients with purpura fulminans and multiple organ failure caused by Neisseria meningitidis . INTERVENTION: Intravenous administration of PC concentrate (100 IU/kg every 6 to 8 hrs) . MEASUREMENTS AND MAIN RESULTS: The administration of PC resulted in normal or above normal levels of the plasma PC activity in all patients . The laboratory and clinical parameters reflecting the severity of coagulopathy improved during the treatment, as did peripheral ischemia and the clinical manifestations of multiple organ failure . No adverse events were noted . One patient died of cerebral edema . CONCLUSION: The administration of PC had a beneficial effect on coagulopathy and peripheral gangrene formation associated with meningococcal disease and showed no adverse effects.
 J Immunol, 1998 May 15, 160(10), 5028 - 36
 Bactericidal monoclonal antibodies that define unique meningococcal B polysaccharide epitopes that do not cross-react with human polysialic acid; Granoff DM et al.; The poor immunogenicity of the Neisseria meningitidis group B polysaccharide capsule, a homopolymer of alpha(2-->8) sialic acid, has been attributed to immunologic tolerance induced by prenatal exposure to host polysialyated glycoproteins . Substitution of N-propionyl (N-Pr) for N-acetyl groups on the meningococcal B polysaccharide, and conjugation of the resulting polysaccharide to a protein carrier, have been reported to yield a conjugate vaccine that elicits protective Abs with minimal autoantibody activity . To characterize the protective epitopes on the derivatized polysaccharide, we isolated 30 anti-N-Pr meningococcal B polysaccharide mAbs . These Abs were heterogeneous with respect to complement-mediated bactericidal activity, fine antigenic specificity, and autoantibody activity as defined by binding to the neuroblastoma cell line, CHP-134, which expresses long-chain a(2-->8)-linked polysialic acid . Eighteen of the Abs could activate complement-mediated bacteriolysis . Seven of these 18 Abs cross-reacted with N-acetyl meningococcal B polysaccharide by ELISA and had strong autoantibody activity . Thus, N-Pr meningococcal B polysaccharide conjugate vaccine has the potential to elicit autoantibodies . However, 7 of the 18 bactericidal mAbs had no detectable autoantibody activity . These Abs may be useful for the identification of molecular mimetics capable of eliciting protective Abs specific to the bacteria, without the risk of evoking autoimmune disease.
 Electrophoresis, 1998 Apr, 19(4), 593 - 6
 Microevolution during epidemic spread of Neisseria meningitidis; Achtman M; Similar to many other naturally transformable bacteria, Neisseria meningitidis has yielded many examples where horizontal genetic exchange has resulted in genetic variation of individual strains . Epidemic strains are purified of genetic variants due to bottlenecks during the spread from country to country, resulting in clonal descent . Occasionally, clonal replacement also occurs during epidemic spread . These processes occur rapidly in serogroup A meningococci; such that after their descent from a common ancestor, clonally related bacteria have diversified at numerous loci within the last decades.
 Electrophoresis, 1998 Apr, 19(4), 577 - 81
 Comparison of the genome organization of pathogenic neisseriae; Bautsch W; Current efforts to completely sequence the meningococcal and gonocococcal genomes raise the question whether the lessons learned from the sequenced strains may be safely extrapolated to other members of these species, or whether, in view of the fact that Neisseriae are highly recombinogenic and exhibit a high degree of horizontal intra- and interspecies genetic transfer, only clone-specific conclusions are valid . From the known physical and genetic maps of each of two gonococcal and meningococcal strains, it would appear that both species exhibit a species-specific conservation in their genetic organization while the interspecies comparison revealed several rearrangements, although still with a high overall similarity . However, these data contrast with other evidence suggesting intra-species rearrangements, such as the nonconserved I-CeuI macrorestriction patterns of different meningococcal and other neisserial strains . Since I-CeuI cuts within the 23S-rRNA sequence, the restriction pattern should give reliable information on the distribution of rrn loci in the neisserial genomes . Further studies are warranted to answer these questions.
 An Esp Pediatr, 1997 Nov, 47(5), 466 - 72
 {Multicenter prospective study on severe bacterial meningitis in children}; Casado Flores J et al.; We prospectively studied the epidemiologic, clinic signs and outcome of bacterial meningitis in 125 children who were admitted into a PICU (Pediatric Intensive Care Unit) of 11 hospitals of Spain and whose meningitis was diagnosed between May 1994 and April 1995 . RESULTS: The median age of the children was 3.55 +/- 3.32 years (range 1 month to 16.5 yrs) . Eighty-eight were bacterial meningitis, probably bacterial 30 and aseptic 7 . The most frequently isolated organisms were N . meningitidis (52), H . influenza type b (17) and S . pneumoniae (8) . Twenty-five percent of N . meningitidis had C serotype . Incidence rate of each germen was depending of age . All patients diagnosed of H . influenza type b meningitis were less than 3 years old . H . influenza type b and meningococcus had similar incidence rate during the first year of life (27% versus 31%) . During the first three years of life H . influenza type b produced one third of bacterial meningitis . A mortality rate of 5.6% (seven patients: 3 S . pneumoniae, 1 N . meningitidis, 1 H . influenza type b and 2 unknown germen) was observed . Patients who die had lower Glasgow coma score (p = 0.034) and seizures (p = 0.001) at admission . At discharge of PICU, 9 survivors (7.2%) had sequelae: mental retardation in 7 patients and hearing loss in two . One third of patients needed hemodynamic support and a 15% of them ventilatory support . CONCLUSIONS: Age is an important epidemiological factor in the etiology of pediatric acute meningitis . H . influenza type b and N . meningitidis had similar incidence rate during the first year of life . S . pneumoniae had the highest mortality rate (37.5%) . The presence of coma and seizures at admission were associated with mortality.
 Dev Biol Stand, 1998, 92, 269 - 76
 Influence of several adjuvants on the immune response against a recombinant meningococcal high molecular weight antigen; Gonzalez S et al.; Studying outer membrane proteins as vaccine candidates, our group has previously isolated, cloned, and expressed in Escherichia coli the gene encoding for a high molecular weight protein (P64k), common to many meningococcal strains . To continue the characterisation of this meningococcal antigen, we have evaluated its immunogenicity in mice alone or combined with several commercially-available adjuvants . We used as an adjuvant aluminium hydroxide (Alhydrogel and Rehydragel), aluminium phosphate, Algammulin, crude saponin, the saponin Quil A, dimethyl-dioctadecyl ammonium bromide (DDA), Freund's adjuvant, and Montanide 888 . The antibody titres against the recombinant protein and whole meningococci elicited with these adjuvants were compared . We found that Quil A produced the highest titres against the recombinant P64k . Algammulin and the quaternary ammonium compound DDA induced the highest levels of antibodies against meningococci . We analysed the recognition of a set of linear peptides by antisera prepared against the protein combined with some of the adjuvants . The responses depended on the adjuvant used and the results have been confirmed by epitope mapping using overlapping peptides synthesised on pins.
 J Immunol, 1998 Feb 1, 160(3), 1509 - 13
 A non-sense mutation at Arg95 is predominant in complement 9 deficiency in Japanese; Horiuchi T et al.; Deficiency of the ninth component of complement (C9D) is one of the most common genetic abnormalities in Japan, with an incidence of one homozygote in 1000 . Although C9D individuals are usually healthy, it has been shown that they have an significantly increased risk of developing meningococcal meningitis . In the present study we report the molecular bases for C9D in 10 unrelated Japanese subjects . As a screening step for mutations, exons 2 to 11 of the C9 gene were analyzed using exon-specific PCR/single-strand conformation polymorphism analysis, which demonstrated aberrantly migrating DNA bands in exon 4 in all the C9D subjects . Subsequent direct sequencing of exon 4 of the C9D subjects revealed that eight of the 10 C9D subjects were homozygous for a C to T transition at nucleotide 343, the first nucleotide of the codon CGA for Arg95, leading to a TGA stop codon (R95X) . R95X is a novel mutation different from those recently identified in a Swiss family with C9D . Cases 6 and 7 were heterozygous for the R95X mutation . Family study in case 10 confirmed the genetic nature of the defect . In case 6, the second mutation for C9D of the C9 gene was identified to be the substitution of Cys to Tyr at amino acid residue 507 (C507Y), while the genetic defect(s) in the other allele in case 7 remains unknown . Our results indicate that a novel mutation, R95X, is present in most cases of C9D in Japan.
 Mol Microbiol, 1998 Mar, 27(6), 1203 - 12
 Neisseria meningitidis producing the Opc adhesin binds epithelial cell proteoglycan receptors; de Vries FP et al.; Neisseria meningitidis possesses a repertoire of surface adhesins that promote bacterial adherence to and entry into mammalian cells . Here, we have identified heparan sulphate proteoglycans as epithelial cell receptors for the meningococcal Opc invasin . Binding studies with radiolabelled heparin and heparin affinity chromatography demonstrated that Opc is a heparin binding protein . Subsequent binding experiments with purified 35SO4-labelled epithelial cell proteoglycan receptors and infection assays with epithelial cells that had been treated with heparitinase to remove glycosaminoglycans confirmed that Opc-expressing meningococci exploit host cell-surface proteoglycans to gain access to the epithelial cell interior . Unexpectedly, Opa28-producing meningococci lacking Opc also bound proteoglycans . These bacteria also bound CEA receptors in contrast to the Opc-expressing phenotype, suggesting that Opa28 may possess domains with specificity for different receptors . Opa/Opc-negative meningococci did not bind either proteoglycan or CEA receptors . Using a set of genetically defined mutants with different lipopolysaccharide (LPS) and capsular phenotype, we were able to demonstrate that surface sialic acids interfere with the Opc-proteoglycan receptor interaction . This effect may provide the molecular basis for the reported modulatory effect of capsule and LPS on meningococcal adherence to and entry into various cell types.
 J Accid Emerg Med, 1998 Mar, 15(2), 102 - 4
 Notification of infectious diseases by junior doctors in accident and emergency departments; Spedding RL et al.; OBJECTIVE: To assess the knowledge about notifiable infectious diseases by accident and emergency (A&E) senior house officers . METHODS: A telephone questionnaire of senior house officers was carried out over a one week period at the end of their six month attachment in A&E departments in Northern Ireland . RESULTS: 81 (91%) of the senior house officers participated in the study; 23 (29%) realised that the doctor diagnosing the notifiable disease had a statutory duty to notify that disease; nine (11%) were aware there were three statutory lists in the United Kingdom . Knowledge about which infectious diseases require notification varied from 79/81 (98%) for meningococcal disease to 15/91 (19%) for methicillin resistant S aureus . Seventy nine (98%) of the doctors thought that a poster displayed in the A&E department would be helpful . There was no significant difference between duration of qualification and performance on the questionnaire (p = 0.2) . CONCLUSIONS: Despite varying experience, junior doctors in A&E do not know which infectious diseases are notifiable by statute . They felt that it would be helpful to have a poster in the A&E department listing the notifiable diseases of that region . To encourage accurate reporting, interregional variation between the statutory lists should be abolished and replaced by one nationally agreed list.
 Vaccine, 1998 Apr, 16(6), 630 - 6
 Pneumococcal conjugate vaccination in adults: circulating antibody secreting cell response and humoral antibody responses in saliva and in serum; Nieminen T et al.; The results from our previous study showed IgA dominated ASC responses to pneumococcal polysaccharide vaccine and to pneumococcal polysaccharide meningococcal outer membrane protein conjugate vaccine (PncOMPC) in adult volunteers . The results indicated that a high IgA ASC response is a useful indicator of a secretory IgA response in saliva . We believe that the mucosal immune responses is potentially an important characteristic of the pneumococcal vaccines and should thus be measured when the new pneumococcal conjugate vaccines are evaluated . In the present study, we studied two new tetravalent pneumococcal conjugate vaccines: the diphtheria toxoid and tetanus toxoid conjugates . In contrast to PncOMPC, these conjugates induced higher responses than the polysaccharide vaccine . Furthermore, the different structure of the two conjugate vaccines might affect the nature of the response . Thus a different vaccine may be optimal for induction of a mucosal response than is of systemic responses.
 Dev Biol Stand, 1998, 92, 323 - 33
 Effect of aluminium hydroxide and meningococcal serogroup C capsular polysaccharide on the immunogenicity and reactogenicity of a group B Neisseria meningitidis outer membrane vesicle vaccine; Rosenqvist E et al.; Three different formulations of an outer membrane vesicle (OMV) vaccine against group B meningococcal disease have been prepared and tested for immunogenicity and reactogenicity in adult volunteers . The vaccines were prepared with or without aluminium hydroxide and serogroup C-polysaccharide (C-ps) . Doses from 12.5 to 100 micrograms protein were given twice at a six weeks' interval . All three formulations were well tolerated and highly immunogenic, inducing bactericidal and opsonizing antibodies in humans . Adsorption of OMVs to aluminium hydroxide reduced the pyrogenicity in rabbits . The differences in immunogenicity between the formulations were relatively small, but after the second dose a stronger booster response was observed when the vaccines were adsorbed .
Thus, a formulation with OMVs and C-ps represents a safe and highly immunogenic vaccine, even without aluminium hydroxide.

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vedi: Bibliografia sui danni neurologici (meningite ed altro) da Vaccino