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+ 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
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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
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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