|
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
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
http://healthimpactnews.com/2014/cdcs-purchase-of-4-billion-of-vaccines-a-conflict-of-interest-in-overseeing-vaccine-safety/
L’INCUBO "MENINGITE",
il presunto nuovo TEST che invece “CREA”
e diffonde, assieme ai
VACCINI Pediatrici, l’EPIDEMIA.
DATI OMESSI e VERITÀ NON DICHIARATE, e NASCOSTE, e cosi
la FRODE sui VACCINI CONTINUA....:
http://www.vacciniinforma.it/?p=4185
Abstract
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.
|
