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MENINGITE e VACCINI - Bibliografia
(English) -  Pag. 4

Continua in: Pag. 1 - Pag. 2 -  Pag. 3 - 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

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.

Dev Biol Stand
, 1998, 92, 127 - 33
 Towards a nasal vaccine against meningococcal disease, and prospects for its use as a mucosal adjuvant; Haneberg B et al.;
A Norwegian outer membrane vesicle (OMV) vaccine against group B meningococcal disease proved to be strongly immunogenic when administered intranasally in mice . The OMV preparation, made from Neisseria meningitidis and intended for parenteral use, was therefore given without adjuvant to human volunteers (n = 12) in the form of nose drops or nasal spray . Such immunizations, which were carried out at weekly intervals during a three-week period, were able to induce systemic antibodies with bactericidal activity in more than half of the individuals . In addition, all vaccinees developed marked increases in OMV-specific IgA antibodies in nasal secretions . The potential of the OMV particles as carriers for other less immunogenic antigens were elucidated in mice with use of whole inactivated influenza virus . Even though influenza virus alone did induce some systemic and salivary antibody responses after being administered intranasally, these responses were greatly augmented when the virus was presented together with OMVs . Thus, it is possible that a nasal OMV vaccine may induce protection against invasive meningococcal disease, and also that it might be used as a vehicle for nasal vaccines against other diseases.
 Pediatr Allergy Immunol, 1997 Nov, 8(4), 194 - 9
 Lack of correlation between soluble CD14 and IL-6 in meningococcal septic shock; Arranz E et al.; Meningococcal sepsis is a good model to study the dynamic response of cytokines and other soluble factors in vivo in the early stages of the disease . Levels of soluble CD14, interleukin-6 (IL-6), IL-6 receptor (IL-6R), and C-reactive protein (CRP) have been measured in plasma from 26 children with septic shock (nine of whom had disseminated intravascular coagulation) and from ten control children . All samples were collected at the onset, before treatment, and, when possible, 24 and 48 hours later . At admission, patients had significantly higher levels of IL-6 (p < 0.001) and CRP (p < 0.001), and lower levels of IL-6R (p < 0.005) than normal controls . After 24 hours, there was a significant increase of sCD24 (p < 0.05) and CRP (p < 0.001) . Although IL-6 showed a progressive decline since the onset, its levels were always higher than controls . There was an inverse correlation between IL-6 and both IL-6R (p < 0.001) and CRP (p < 0.001), probably due to the later increase of CRP . Nevertheless, sCD14 did not correlate with IL-6 levels . We have confirmed the finding of IL-6 as a sensitive and reliable inflammatory marker in septic shock . Moreover, the ratio IL-6/IL-6R may have a prognostic value, given a putative role of IL-6R in modulating the effects of IL-6 in meningococcal sepsis.
 Rev Esp Salud Publica, 1997 Mar-Apr, 71(2), 103 - 26
 {Efficacy of the meningococcal vaccine from Group C capsular polysaccharide}; Gonzalez Enriquez J et al.; BACKGROUND: This report is a systematic review of the effect intensity and duration of the immune response to meningococcal serogroup C vaccine . The vaccine safety, efficacy and effectiveness are also analyzed . METHODS: MEDLINE literature search in the period 1970-1996 . Meningoccocal polysaccharide vaccine clinical trials and human prospective studies were specifically searched . Quality of the retrieved studies were analyzed . Information available was integrated . RESULTS: Group C meningoccal polysaccharide vaccine is a safe product . Its efficacy is over 85% among adults and children over 5 years old . 70% (CI 95%: 5-91%) under 5 years old, and 55% among children 2-3 years old . The vaccine is not effective under 2 years . The duration of protective antibody levels decrease with age . The proportion of vaccinated children effectively protected one year after vaccination is low . Vaccination does not affect the immune response to ulterior revaccination . CONCLUSIONS: Group C meningococcal polysaccharide vaccine is indicated in adults and children over 2 years old to protect them from meningococcal disease due to group C when exposed to high risk of infection . The outbreaks control is the main indication for the use of this vaccine . Routine immunization in not outbreak situation is not recommended due to the small vaccine protection in children under 2 years old, the limited efficacy in children under 5, and the short duration of the immunity in children.
 Proc Natl Acad Sci U S A, 1998 Mar 17, 95(6), 3140 - 5
 Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms; Maiden MC et al.; Traditional and molecular typing schemes for the characterization of pathogenic microorganisms are poorly portable because they index variation that is difficult to compare among laboratories . To overcome these problems, we propose multilocus sequence typing (MLST), which exploits the unambiguous nature and electronic portability of nucleotide sequence data for the characterization of microorganisms . To evaluate MLST, we determined the sequences of approximately 470-bp fragments from 11 housekeeping genes in a reference set of 107 isolates of Neisseria meningitidis from invasive disease and healthy carriers . For each locus, alleles were assigned arbitrary numbers and dendrograms were constructed from the pairwise differences in multilocus allelic profiles by cluster analysis . The strain associations obtained were consistent with clonal groupings previously determined by multilocus enzyme electrophoresis . A subset of six gene fragments was chosen that retained the resolution and congruence achieved by using all 11 loci . Most isolates from hyper-virulent lineages of serogroups A, B, and C meningococci were identical for all loci or differed from the majority type at only a single locus . MLST using six loci therefore reliably identified the major meningococcal lineages associated with invasive disease . MLST can be applied to almost all bacterial species and other haploid organisms, including those that are difficult to cultivate . The overwhelming advantage of MLST over other molecular typing methods is that sequence data are truly portable between laboratories, permitting one expanding global database per species to be placed on a World-Wide Web site, thus enabling exchange of molecular typing data for global epidemiology via the Internet.
 Intensive Care Med, 1998 Feb, 24(2), 157 - 61
 A normal platelet count at admission in acute meningococcal disease does not exclude a fulminant course; Van Deuren M et al.; OBJECTIVE: To determine the value of the platelet count at admission for the assessment of the severity of disease in acute meningococcal infections . DESIGN: Retrospective and prospective, descriptive patient study . SETTING: University Hospital Intensive Care Unit (ICU) . PATIENTS: All patients (n = 92) with acute meningococcal disease from 1985 to 1997, who arrived at the ICU within 12 h after hospital admission and had more than one platelet count during the first 12 h . MEASUREMENTS AND RESULTS: After admission, platelets dropped in 95% of the patients . At admission, 2/41 (5%) of the non-hypotensive patients and 13/51 (25%) of the hypotensive patients had platelets fewer than 100 x 10(9)/l . During the following 12 h, these percentages increased to 15% and 71%, respectively . Fatalities had, at admission, a median platelet count of 111 x 10(9)/l (range, 19-302 x 10(9)/l), whereas the nadir, occurring at median 7.0 h (range, 1.3-12 h), was 31 x 10(9)/l (range, 12-67 x 10(9)/l) . Plasma TNF, measured shortly after admission, correlated better with the platelet nadir (r = -0.65, p < 0.0001) than with the platelet count at admission . Similarly, serum lactate correlated better with the platelet nadir . CONCLUSIONS: As platelets drop after admission, the use of the platelet count at admission for the assessment of the prognosis in acute meningococcal disease may be misleading . Frequently repeated platelet counts are a better tool for evaluating the severity of disease.
 Pathol Biol (Paris), 1997 Nov, 45(9), 729 - 36
 Epidemiological survey of Neisseria meningitidis susceptibility to penicillin G in France; Guibourdenche M et al.; The susceptibility of 82 strains of Neisseria meningitidis to penicillin G and amoxicillin was evaluated with two media "gonococci-meningococci" medium (G medium) derived from Mueller Hinton and chocolate agar . Among these 82 strains 52 were isolated from CSF and/or blood and 30 from miscellaneous isolates . G medium was compared with chocolate agar using the correlation between diameters and MIC and the E-test . Routinely standardised antibiogram is still used but the authors added the following techniques 1) MIC of penicillin G is tested (0.06; 0.125; 0.250; 0.50 mg/l); 2) use of oxacillin disc charged with 5 micrograms . Penicillinase producing meningococci were not found . Standardised antibiogram on 4192 strains resulted in a modal distribution of diameters between 18 to 40 mm . Moderate meningococci susceptible strains to penicillin G are increasing in France: 1994: 4%; 1995: 11%; 1996: 18%.
 Arch Dis Child, 1998 Jan, 78(1), 58 - 60
 Preliminary clinical evaluation of meningococcal disease and bacterial meningitis by ultrasonic enhancement; Barnes RA et al.; Antigen detection in the urine and serum may be useful in the diagnosis of suspected meningococcal disease, especially after previous antibiotic treatment . Current test card procedures using commercial agglutination kits are often too insensitive to contribute to diagnosis . Diagnosis of meningococcal disease rose from 37% with the test card procedure to 74% following ultrasonic enhancement.
 Infect Immun, 1998 Apr, 66(4), 1334 - 41
 Intranasal administration of a meningococcal outer membrane vesicle vaccine induces persistent local mucosal antibodies and serum antibodies with strong bactericidal activity in humans; Haneberg B et al.; A nasal vaccine, consisting of outer membrane vesicles (OMVs) from group B Neisseria meningitidis, was given to 12 volunteers in the form of nose drops or nasal spray four times at weekly intervals, with a fifth dose 5 months later . Each nasal dose consisted of 250 microg of protein, equivalent to 10 times the intramuscular dose that was administered twice with a 6-week interval to 11 other volunteers . All individuals given the nasal vaccine developed immunoglobulin A (IgA) antibody responses to OMVs in nasal secretions, and eight developed salivary IgA antibodies which persisted for at least 5 months . Intramuscular immunizations did not lead to antibody responses in the secretions . Modest increases in serum IgG antibodies were obtained in 5 volunteers who had been immunized intranasally, while 10 individuals responded strongly to the intramuscular vaccine . Both the serum and secretory antibody responses reached a maximum after two to three doses of the nasal vaccine, with no significant booster effect of the fifth dose . The pattern of serum antibody specificities against the different OMV components after intranasal immunizations was largely similar to that obtained with the intramuscular vaccine . Five and eight vaccinees in the nasal group developed persistent increases in serum bactericidal titers to the homologous meningococcal vaccine strain expressing low and high levels, respectively, of the outer membrane protein Opc . Our results indicate that meningococcal OMVs possess the structures necessary to initiate systemic as well as local mucosal immune responses when presented as a nasal vaccine . Although the serum antibody levels were less conspicuous than those after intramuscular vaccinations, the demonstration of substantial bactericidal activity indicates that a nonproliferating nasal vaccine might induce antibodies of high functional quality.
 Enferm Infecc Microbiol Clin, 1997 Nov, 15(9), 451 - 5
 {Meningococcal meningitis:descriptive study of 76 cases in a pediatric hospital}; Muzzio de Califano G et al.; BACKGROUND: One of the principal causes of bacterial meningitis (BM) in children older than one month is Neisseria meningitidis (Nm) . A quick diagnosis and an immediate treatment are considered essential for a good outcome . We propose this study with the purpose of evaluating the clinical and epidemiological characteristics of the patients with BM caused by Nm and analyzing the effect on the presentation and incidence of sequelae and/or complications of the time elapsed since the starting of symptoms and the beginning of the treatment . METHODS: We performed a retrospective analysis of the clinical registers of 76 patients diagnosed as BM caused by Nm entered in the Hospital de Pediatria Pedro de Elizalde, Buenos Aires, Argentina, during the years 1992 and 1993 . We investigated age, sex, date of entrance, first symptoms, biochemistry of cerebrospinal fluid (CSF), nutritional status, convulsions and/or complications, length of internation and conditions at discharge . Processing was done with Epi-info 5.0 . Differences between qualitative variables were analyzed with chi 2 and differences between means with z-test . RESULTS: Boys were majority; fever was the most frequent initial symptom; petechiae were less frequently found, specially among infants . 79% of the patients had CSF of purulent characteristics; 32.9% of the patients had complications during their evolution; its incidence raised up to 48% in infants . Lethality was 1.3%, 6.5% of the children had sequelae at the moment of discharge . The average time of internment was 13 days . There were no significant differences when different groups were compared according to their prior evolution time . CONCLUSIONS: 1) Petechiae and vomits were significantly less frequent in infants; 2) the incidence of complications was significantly higher in this last group; 3) no greater incidence of complications or sequelae was observed in patients whose previous period of evolution was longer than 48 hours; 4) in all groups of age we found insidious forms of starting, and 5) there were patients with CSF of normal biochemical characteristics in all groups considered independently of the time of evolution elapsed.
 Enferm Infecc Microbiol Clin, 1997 Dec, 15(10), 510 - 4
 {Clinical and epidemiologic study of meningococcal meningitis in the health region of Santiago de Compostela (1990-1997)}; Juncal AR et al.; BACKGROUND: The aim of this study was to determine the clinico-epidemiologic characteristics of meningitis caused by Neisseria meningitidis . METHODS: A retrospective study was performed of the bacterial meningitis with LCR positive cultures for Neisseria meningitidis from January 1990 to 31 March, 1997 . To calculate the rate of incidence data from the 1990 population census were used corresponding to a population of 465,786 inhabitants per year attended in our hospital . RESULTS: A growth was observed in the strains of N . meningitidis in 61 LCR, representing 30% of all positive LCRs . Thirty-three strains belonged to serogroup B (54%) and 28 of serogroup C (46%) . Ninety-one point nine percent of the cases were found in patients under the age of 20 . The annual rates of incidence ranged from 2.3 cases/100,000 inhabitants in 1990 to 3.4 cases/100,000 inhabitants in 1996 with a slight decrease between these two dates . In patients under the age of 15 years, the rates of incidence ranged from 12.3/100,000 in 1990 to 13.4 per 100,000 inhabitants in 1996 . In the remaining years the rates decreased with a minimum of 2.2 cases/100,000 inhabitants . The incidence for N . meningitis serogroup C ranged from 0 to 0.9 cases/100,000 inhabitants between 1990 and 1995 . In 1996 the rate increased up to 2.6 cases/100,000 inhabitants . The rate of mortality was 6.6% and sequelae 8.7% . Since 1995 strains with decreased sensitivity to penicillin have been isolated, with percentages ranging from 20% to 56.25% . All strains remained sensitive to third generation cephalosporins and rifampicin . CONCLUSIONS: Neisseria meningitidis remains the most frequent etiologic agent of acute bacterial meningitis . The increase in serogroup C strains and the ever more frequent appearance of strains with decreased resistance to penicillin are confirmed, as is the persistence of high levels of endemia in our medium.
 South Med J, 1998 Mar, 91(3), 287 - 8
 Meningococcal cellulitis and sialadenitis; Gelfand MS et al.; Neisseria meningitidis is a rare cause of cellulitis . No cases of meningococcal sialadenitis have previously been reported . We recently successfully treated a patient who had meningococcal cellulitis and sialadenitis . We review previously reported cases of cellulitis due to N meningitidis and speculate on the role of underlying disease in the pathogenesis of this infection.
 Postgrad Med, 1998 Mar, 103(3), 102 - 117
 Bacterial meningitis in children and adults . Changes in community-acquired disease may affect patient care; Phillips EJ et al.; Despite improved understanding of how bacterial meningitis develops, the infection remains a potentially life-threatening emergency capable of causing significant morbidity and mortality . Since the introduction and widespread use of H influenzae type b vaccine in infancy and childhood in North America, the epidemiology of community-acquired bacterial meningitis has changed . S pneumoniae is now the most common cause in children and adults overall, although N meningitidis causes most disease in patients between ages 2 and 18 years . Broad-spectrum cephalosporins (eg, ceftriaxone, cefotaxime) are considered the agents of choice for empirical treatment of bacterial meningitis . However, use of these agents will have to be reconsidered if the incidence of invasive infection from drug-resistant S pneumoniae continues to increase . The role of adjunctive corticosteroid therapy needs to be better defined . Improved conjugate pneumococcal and meningococcal vaccines may soon make bacterial meningitis a preventable disease.
 J Bacteriol, 1998 Mar, 180(6), 1533 - 9
 Characterization of the gene cassette required for biosynthesis of the (alpha1-->6)-linked N-acetyl-D-mannosamine-1-phosphate capsule of serogroup A Neisseria meningitidis; Swartley JS et al.; The (alpha1-->6)-linked N-acetyl-D-mannosamine-1-phosphate meningococcal capsule of serogroup A Neisseria meningitidis is biochemically distinct from the sialic acid-containing capsules produced by other disease-associated meningococcal serogroups (e.g., B, C, Y, and W-135) . We defined the genetic cassette responsible for expression of the serogroup A capsule . The cassette comprised a 4,701-bp nucleotide sequence located between the outer membrane capsule transporter gene, ctrA, and galE, encoding the UDP-glucose-4-epimerase . Four open reading frames (ORFs) not found in the genomes of the other meningococcal serogroups were identified . The first serogroup A ORF was separated from ctrA by a 218-bp intergenic region . Reverse transcriptase (RT) PCR and primer extension studies of serogroup A mRNA showed that all four ORFs were cotranscribed in the opposite orientation to ctrA and that transcription of the ORFs was initiated from the intergenic region by a sigma-70-type promoter that overlapped the ctrA promoter . The first ORF exhibited 58% amino acid identity with the UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) 2-epimerase of Escherichia coli, which is responsible for the conversion of UDP-GlcNAc into UDP-N-acetyl-D-mannosamine . Polar or nonpolar mutagenesis of each of the ORFs resulted in an abrogation of serogroup A capsule production as determined by colony immunoblots and enzyme-linked immunosorbent assay . Replacement of the serogroup A biosynthetic gene cassette with a serogroup B cassette by transformation resulted in capsule switching from a serogroup A capsule to a serogroup B capsule . These data indicate that assembly of the serogroup A capsule likely begins with monomeric UDP-GlcNAc and requires proteins encoded by three other genes found in the serogroup A N . meningitidis-specific operon located between ctrA and galE.
 Mol Microbiol, 1998 Feb, 27(4), 705 - 15
 Consequences of the loss of O-linked glycosylation of meningococcal type IV pilin on piliation and pilus-mediated adhesion; Marceau M et al.; Pili, which are assembled from protein subunits called pilin, are indispensable for the adhesion of capsulated Neisseria meningitidis (MC) to eukaryotic cells . Both MC and Neisseria gonorrhoeae (GC) pilins are glycosylated, but the effect of this modification is unknown . In GC, a galactose alpha-1,3-N-acetyl glucosamine is O-linked to Ser-63, whereas in MC, an O-linked trisaccharide is present between residues 45 and 73 of pilin . As Ser-63 was found to be conserved in pilin variants from different strains, it was replaced by Ala in two MC variants to test the possible role of this residue in pilin glycosylation and modulation of pili function . The mutated alleles were stably expressed in MC, and the proteins they encoded migrated more quickly than the normal protein during SDS-PAGE . As controls, neighbouring Asn-61 and Ser-62 were replaced by an Ala with no effect on electrophoretic mobility . Silver staining of purified pilin obtained from MC after oxidation with periodic acid confirmed the loss of glycosylation in the Ser-63-->Ala pilin variants . Mass spectrometry of HPLC-purified trypsin-digested peptides of pilin and Ser-63-->Ala pilin confirmed that peptide 45-73 has the molecular size of a glycopeptide in the wild type . In strains producing non-glycosylated pilin variants, we observed that (i) no truncated S pilin monomer was produced; (ii) piliation was slightly increased; and (iii) presumably as a consequence, adhesiveness for epithelial cells was increased 1.6- to twofold in these derivatives . In addition, pilin monomers and/or individual pilus fibres, obtained after solubilization of a crude pili preparation in a high pH buffer, were reassociated into insoluble aggregates of pili more completely with non-glycosylated variants than with the normal pilin . Taken together, these data eliminate a major role for pilin glycosylation in piliation and subsequent pilus-mediated adhesion, but they demonstrate that glycosylation facilitates solubilization of pilin monomers and/or individual pilus fibres.
 Rev Saude Publica, 1997 Jun, 31(3), 254 - 62
 {Epidemiological characterization of meningococcal disease in a metropolitan area in Southeastern Brazil, 1976-1994}; Gama SG et al.; INTRODUCTION: Meningococcal disease continues to warrant assessment as to its endemic and epidemic multicausality and temporal trends in various locations . MATERIAL AND METHOD: Based on a standardization of epidemiological investigation of meningococcal disease in the municipality of Rio de Janeiro county, Southeastern Brazil, as from epidemic of the 1970s a study to characterized the epidemiological characteristics of the disease, was realized . The total of 4,155 cases reported between 1976 and 1994 were analyzed in a retrospective, descriptive, and analytical study, using the epidemiological investigation forms issued by the Municipal Health Secretariat . Statistical analysis was performed using the chi 2, Wilcoxon-Mann-Whitney, and Kruskal-Wallis tests . RESULTS: The study resulted in the definition of three periods, classified as post-epidemic (1976-79), endemic (1980-86), and epidemic (1987-94), differentiated by the incidence rates and the predominant meningococcal serogroup . The mean incidence rates per period in the municipality were 3.51, 1.67, and 6.53 cases/ 100,000 inhabitants, respectively . Serogroups A and C predominated during the post-epidemic period, B and A in the endemic, and B in the epidemic . CONCLUSION: The mean case fatality rate remained virtually unchanged over time, but it varied by hospital, and during all three periods was lower in the State government reference hospital than in the other hospitals, whether public or private . The highest incidence and case fatality rates were associated with patients under one year of age, and the risk of acquiring the disease was greater among males . The highest incidence coefficients tended to occur in the same areas of the county during the three epidemiological periods, and the shanty-town population was at twice the risk of acquiring the disease.
 FEMS Immunol Med Microbiol, 1998 Jan, 20(1), 79 - 86
 Bactericidal activity of antibodies elicited against the Neisseria meningitidis 37-kDa ferric binding protein (FbpA) with different adjuvants; Gomez JA et al.; The 37-kDa ferric binding protein, FbpA, from three Neisseria meningitidis strains was purified to homogeneity with iron-affinity chromatography and used for immunisation of mice employing four different adjuvants: aluminium hydroxide, Freund's, the saponin Quil-A, and a Ribi adjuvant system (RAS) . Controls immunised without adjuvant were also included . All sera obtained were monospecific for the meningococcal FbpA, with antibody titres higher when RAS and Quil-A were used (256), PBS resulting in titres similar to those of Freund's (64), and, surprisingly, with no antibodies elicited when aluminium hydroxide, the only approved adjuvant for use in humans, was used . All anti-FbpA sera bound to intact meningococcal cells, showing a complete cross-reactivity, but the bactericidal activity of anti-FbpA antibodies, demonstrated for the first time in this work, was low (32% of killing with the homologous strain), and the analysis of immunoglobulin isotypes showed that the non-bactericidal IgG1 was predominant . The results confirm that the FbpA is surface-exposed, antigenic, and able to elicit bactericidal antibodies, although, in the conditions and with the adjuvants tested, killing efficacy was low and cross-killing was very variable, not supporting the inclusion of this protein in vaccine formulations . Nevertheless, given the high conservation of the FbpA in the genus Neisseria, its surface exposure and its antigenicity, studies on immunisation with peptides corresponding to the exposed epitopes and/or new adjuvant systems could improve the bactericidal response to this protein, making it suitable for vaccine development.
 J Med Microbiol, 1998 Mar, 47(3), 257 - 64
 Differential binding of apo and holo human transferrin to meningococci and co-localisation of the transferrin-binding proteins (TbpA and TbpB); Powell NB et al.; Apo-transferrin (apo-hTf) and holo-transferrin (holo-hTf) were separately conjugated to 15-nm colloidal gold . Iron-restricted Neisseria meningitidis strain SD (B:15:P1.16) bound up to three-fold more holo-hTf than apo-hTf (p <0.001) . The ability of meningococcal mutants lacking either transferrin-binding protein A (TbpA) or TbpB to discriminate between apo-hTf and holo-hTf was also investigated . There was no significant difference between the amount of gold-labelled apo-transferrin bound by the isogenic TbpA mutant (expressing TbpB) and the parent strain, whereas an isogenic TbpB mutant (expressing TbpA) bound significantly less gold-labelled apo-hTf . The isogenic TbpA and TbpB mutants and the parent strain all bound significantly more holo-hTf than apo-hTf, whereas the double 'knock-out' mutant failed to bind hTf irrespective of the iron-loading . In the isogenic mutants, TbpB was more effective in binding either apo- or holo-hTf than TbpA . Monoclonal antibodies against TbpA and TbpB were used to co-localise the transferrin-binding proteins on strain SD . The ratio of TbpA:TbpB was approximately 1:1 . TbpA and TbpB were occasionally observed in close proximity to each other, but the two proteins were generally quite separate, which may indicate that they do not usually form a complex to act as a transferrin receptor.
 Am J Med Genet, 1998 Feb 26, 76(1), 67 - 70
 Nevo syndrome; Dumic M et al.; We report on a patient with Nevo syndrome manifesting intrauterine and postpartum overgrowth, accelerated osseous maturation, dolichocephaly, highly arched palate, large, low-set ears, cryptorchidism, delayed neuropsychological development, hypotonia, adema, contractures of the hands and feet, a single a transverse palmar crease, and tapering digits . After meningococcal sepsis at age 6 months, he remained decerebrate . Thereafter, overgrowth and especially weight gain were extremely accelerated until his death at age 18 months, at which time his height was 103 cm and his weight was 23 kg . In addition to low plasma concentrations of growth hormone and insulin-like growth factor, severe insulin resistance was observed . It is presumed that a selective defect in insulin-stimulated glucose uptake, with preservation of anabolic effect, was one of the causes of his "overgrowth without growth hormone," at least in the last 12 months of life after severe brain damage.
 Bull Soc Pathol Exot, 1997, 90(5), 299 - 302
 {Chronical of a declared meningococcal meningitis epidemic (Goma, Zaire, August 1994)}; Niel L et al.; The authors relate their experience controlling an epidemic of meningitis which broke out in the refugee camps of the Goma region, in northern Zaire, after the dramatic events which had happened in Rwanda in April and June 1994 . Out of the 348 cases of purulent meningitis diagnosed by the Bioforce team, meningococcal etiology was confirmed 327 times . The isolated meningococci were all of the serogroup A, serotype A; 4; P 1,9 . They were resistant to streptomycin and to sulphamides . The epidemic lasted one month, touched people of all ages and spread progressively to all the camps . The epidemic surveillance set up meant that vaccination was carried out very quickly and the epidemic brought rapidly under control, even if other factors did intervene . All those called upon to intervene in such a context should be made aware of the interest of the basic triad to fight these epidemics: rapid vaccination, treatment of cases with oily chloramphenicol and bio-epidemiological surveillance.
 J Pediatr Nurs, 1998 Feb, 13(1), 32 - 40
 Sleep as an indicator for pain relief in an infant: a case study; Gedaly-Duff V et al.; Sleep was used as an indicator of pain relief for an 8-month-old female infant with meningococcemia who experienced nociceptive input from skin wounds and multiple noxious treatment procedures during her recovery . A sleep activity record documented total hours of sleep, awake/crying, awake/content, and longest hours of sleep after nonanalgesic and analgesic interventions to mediate the infant's pain . Sleep appears to be a useful indicator of the efficacy of pain treatment for infants.
 FEMS Microbiol Lett, 1998 Feb 15, 159(2), 209 - 14
 siaD PCR ELISA for confirmation and identification of serogroup Y and W135 meningococcal infections; Borrow R et al.; Non-culture diagnosis and serogroup determination of meningococcal infection is important in contact management where vaccination may be possible . A serogroup B and C PCR ELISA assay for the non-culture diagnosis and serogroup determination has proved invaluable for enhanced epidemiological surveillance and contact management . A polymerase chain reaction assay, based on a restriction fragment length polymorphism in the meningococcal serogroup Y and W135 sialyltransferase (siaD) gene, was developed to enhance the range of non-culture diagnosis of meningococcal infection from clinical samples . The PCR assay was adapted to an ELISA format incorporating hybridisation with serogroup-specific Y and W135 oligonucleotide probes . The serogroup-specific W135 and Y PCR ELISA is a useful addition to currently available serogroup B and C assay for non-culture diagnosis of meningococcal infection and outbreak investigation.
 Sante, 1997 Nov-Dec, 7(6), 384 - 90
 {An epidemic of meningococcal meningitis in the region of Savanes in Togo in 1997: research and control strategies}; Aplogan A et al.; Neisseria meningitidis is responsible for high levels of morbidity and mortality in the developing countries of the African meningitis belt . There are frequent meningococcal meningitis epidemics in this region affecting almost 1,000 people in every 100,000 (1%) . Epidemics generally occur during the dry season but the interval between epidemics is variable (between 2 and 25 years) . The reasons for these recurrent epidemics are unclear . There is a safe and effective polysaccharide vaccine against meningococci A and C . Unfortunately, the immunity it provides decreases with time, especially in young children (aged less than 5 years) and it is thus not included in the Expanded Program on Immunization (EPI) . WHO recommends mass vaccination using a threshold approach . This control strategy is effective if vaccination begins very soon after the threshold is crossed . There was an outbreak of group A meningococcal meningitis in the Savanes region of northern Togo in December 1996 . The national surveillance system put out an alert and control measures were implemented . These involved improvement of the surveillance system, and containment immunization in villages for early cases followed by a mass immunization campaign in the entire region, distribution of oily chloramphenicol and decentralized case management . The target population for mass vaccination included everyone older than 6 months of age living in the Savanes region . The aim was to vaccinate at least 80% of the target population . There were 2,992 cases of meningitis reported in the Savanes region between December 1996 and May 1997 (in a population of about 500,000) . This gives a cumulative incidence rate of 581 per 100,000 population . The epidemic was bimodal, with the first peak in the number of cases occurring at the end of January and the second peak in March . There were 60,700 vaccinations in two of the four districts of the region in December and January, as part of the containment strategy and 346,469 vaccinations in the four districts of the region during February, as part of the mass vaccination campaign . By the end of the mass campaign, 67.3% of the target population in the region as a whole had been vaccinated, with 61% vaccinated in the Kpendjal district and 78% in the Oti district . There was an increase in the number of cases 2 weeks after the end of the mass vaccination campaign . This was attributed to the inadequate level of vaccination achieved . Only 52% of the urban population of Dapaong were vaccinated . The national surveillance system put out an alert early in the epidemic . The intervention was planned and adapted according to the progression of the epidemic, and national and international efforts were well coordinated . This emphasizes the importance of a rapid reaction from the surveillance system and of the choice of strategy for dealing with meningitis epidemics in sub-Sahelian Africa.
 J Infect Dis, 1998 Mar, 177(3), 683 - 91
 Immunogenicity of two efficacious outer membrane protein-based serogroup B meningococcal vaccines among young adults in Iceland; Perkins BA et al.; Serum bactericidal activity (SBA) and ELISA antibody levels elicited by two efficacious serogroup B meningococcal vaccines were measured in a controlled trial involving 408 15- to 20-year-olds . Subjects were given two doses at a 6-week interval of a serogroup B or control vaccine . Response was defined as > or = 4-fold rise in antibody level . After two doses of the Finlay Institute (Havana) vaccine at 12 months, the proportions of SBA and ELISA responders were not different from those of the control group (15% and 17% {vaccine} vs . 13% and 9% {control}, P > .05) . After two doses of the National Institute of Public Health (Oslo) vaccine, there were more SBA and ELISA responders than in the control group (47% and 34% {vaccine} vs . 10% and 1% {control}) or the Finlay Institute vaccine group (P < .05 for both) . SBA and ELISA may be insensitive correlates for protective efficacy for some outer membrane protein-based serogroup B meningococcal vaccines.
 Gac Sanit, 1997 Sep-Oct, 11(5), 242 - 51
 {Analysis of the management of the vaccination campaign in 1996-1997 against meningococcus C in Galicia}; Farjas P et al.; This paper describes the process to design and plan a vaccination campaign against group C N . Meningitidis developed in the Autonomous Community of Galicia between December 9, 1996 and January 31, 1997 . We also analyse the results of this process in terms of management results, vaccine coverage and preliminary estimates of effectiveness . A Work group was established, made up of professionals in charge of different intervention areas . A person was designated in charge of the whole campaign and a follow-up and information system was created . The work plan consisted of daily meetings for follow-up, co-ordination and task distribution; and periodical meetings with primary health care and peripheral public health coordinators . Strategies of implantation--in order to make sure the campaign accessibility and acceptability; of budget and of communication with health workers, inhabitants and mass media were developed . Up to 100 tasks were identified to develop the technical information and logistic activities: mailings, meetings, leaflets, ...; purchasing of 584.980 doses of vaccine, supplying to 715 vaccination points (1040 deliveries); problem solving and intervention recording . A vaccination coverage of 85% was achieved, with notification of 8 adverse reactions and 6 errors in the administration of the vaccine (34 children affected) . The strategy chosen for the design and planning of the campaign has proven to be effective and valid and sufficient to achieve the final goals, in due time and without problems of misinformation, shortage of vaccine or lack of participation of professionals or people . Mistakes due to incorrect administration of the vaccine, management problems, rupture of the cold chain or recording failures were minimal and accidental.
 East Afr Med J, 1997 Jul, 74(7), 423 - 6
 Clinical predictors of epidemic outcome in meningococcal infection in Jos, Nigeria; Angyo IA et al.; The clinical predictors of outcome in children admitted into the Emergency Paediatric Unit at the Jos University Teaching Hospital with meningococcal infection during an out-break of the disease (between February-April 1996) were studied . Eighty seven children were admitted with meningococcal infection during the period . There were 60 males and 27 females (M:F = 2.2:1), aged between five weeks and 16 years (mean 7.7 +/- 4.9 years) . Overall mortality was 26.4 per cent . Eighty five per cent of the patients who presented in shock died, compared with nine per cent who presented without shock (p < 0.000001) . Similarly, 65% of the patients who presented in coma died, compared with 12.5% who did not present in coma (p < 0.000001) . Other factors associated with a poor outcome included age one year and below, petechial/purpuric rash on presentation and meningococcaemia . Complications were documented in 27 (31.0%) of the patients, consisting mainly of deafness, extensive vasculitis/ulceration of extremities, gangrene of legs hemiparesis and cranial nerve palsies.
 Shock, 1998 Feb, 9(2), 138 - 42
 Activated protein C concentrate for the treatment of meningococcal endotoxin shock in rabbits; Roback MG et al.; To evaluate the effects of activated protein C therapy in a rabbit model of meningococcal endotoxin-induced shock, we performed a prospective, blinded, placebo-controlled animal trial . Forty New Zealand White rabbits were challenged with intravenous meningococcal endotoxin (lipooligosaccharide) 100 microg/kg . Ten minutes before endotoxin challenge, animals were administered either activated protein C 1600 microg/mL (n = 20) or an equal volume of saline (n = 20) as an initial bolus . After endotoxin challenge, activated protein C treated animals were administered a continuous infusion of activated protein C 160 microg/kg/h and saline-treated animals were administered an equal volume infusion of saline . Both activated protein C treated and saline control animals demonstrated evidence of shock after endotoxin challenge; mean arterial pressure and serum bicarbonate significantly (p < .01) declined, and heart rate significantly (p < .01) increased from baseline . In activated protein C treated animals, mean plasma activated protein C activity was 5.69 microg/mL (+/- 3.2) 1 h after challenge, whereas plasma protein C activity was not detected in controls . Mean prothrombin and activated partial thromboplastin times were significantly (p < or = .01) prolonged compared with saline-treated controls . Other hematologic and chemical measurements did not differ between groups . Fifteen of 20 (75%) animals treated with activated protein C concentrate survived to 24 h, while 9 of 20 (45%) control animals survived to 24 h (p = .05) . Those animals treated with activated protein C had improved survival, which corroborates the findings of early clinical studies in which replacement of protein C improved outcome.
 Infect Immun, 1998 Mar, 66(3), 1028 - 36
 Nonopsonic phagocytosis of group C Neisseria meningitidis by human neutrophils; Estabrook MM et al.; Although complement-mediated bactericidal activity in serum has long been known to be very important in host defense against Neisseria meningitidis, recent studies have shown that opsonic phagocytosis by neutrophils is also important . The purpose of this study was to determine if endemic group C N . meningitidis strains were susceptible to nonopsonic (complement- and antibody-independent) phagocytosis by human neutrophils, which is a well-described phenomenon for Neisseria gonorrhoeae . Gonococci that possess one or more of a group of heat-modifiable outer membrane proteins (called opacity-associated {Opa} proteins) are phagocytosed by neutrophils in the absence of serum . We found that four serogroup C meningococcal strains bearing the lacto-N-neotetraose (LNnT) structure on lipooligosaccharide (LOS) were phagocytosed by neutrophils in the absence of antibody and active complement . Confocal microscopy confirmed that the organisms were internalized by neutrophils . This susceptibility was not restricted to carrier isolates, since two of the strains were cultured from blood or cerebrospinal fluid . All four strains expressed Opa protein and had relatively less endogenous LOS and capsule sialylation compared to six strains that were resistant to this type of phagocytosis . Nonopsonic phagocytosis of two of the four strains was inhibited by exogenous sialylation of LOS LNnT and the binding of monoclonal antibody to LNnT . However, an isogenic mutant that lacked the LNnT structure was fully susceptible to nonopsonic phagocytosis . We conclude that group C meningococci can be phagocytosed by neutrophils in the absence of antibody and active complement possibly by two different mechanisms . Expression of Opa protein and downregulation of endogenous surface sialic acids analogous to what is seen for N . gonorrhoeae might be necessary for N . meningitidis as well.
 Infect Immun, 1998 Mar, 66(3), 959 - 65
 Human T-cell responses after vaccination with the Norwegian group B meningococcal outer membrane vesicle vaccine; Naess LM et al.; We have analyzed human T-cell responses in parallel with serum immunoglobulin G (IgG) antibody levels after systemic vaccination with the Norwegian group B Neisseria meningitidis outer membrane vesicle (OMV) vaccine . Ten adult volunteers, with no or very low levels of serum IgG antibodies against meningococci, received three doses intramuscularly of the OMV vaccine (at weeks 0, 6, and 46) . T-cell proliferation against the OMV vaccine, purified outer membrane proteins (PorA and PorB), and control antigens (Mycobacterium bovis BCG vaccine and tetanus toxoid) was measured by thymidine incorporation of peripheral blood mononuclear cells before and after vaccination . The results showed that vaccination with OMV elicits strong primary and booster T-cell responses specific to OMV as well as the PorA (class 1) protein and significant, but markedly lower, responses against the PorB (class 3) protein . The median responses to OMV and PorA were 26 and 16 times the prevaccination levels, respectively . Most of the vaccinees showed low T-cell responses against OMV and PorA before vaccination, and the maximum T-cell responses to all vaccine antigens were usually obtained after the second vaccine dose . We found a positive correlation between T-cell responses and anti-OMV IgG antibody levels (r = 0.50, P < 0.0001, for OMV and PorA) . In addition, we observed a progressive increase in the percentage of CD45R0+ (memory) CD4-positive T cells (P = 0.002) . In conclusion, we have shown that the Norwegian OMV vaccine against meningococcal B disease induced antigen-specific T-cell responses, kinetically accompanied by serum IgG responses, and that vaccination increased the proportion of memory T-helper cells.