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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
Lancet, 1998 Mar 28, 351(9107), 950 - 3
Anti-inflammatory cytokine profile and mortality in
febrile patients; van Dissel JT et al.;
BACKGROUND: An
anti-inflammatory cytokine profile on whole-blood
stimulation in vitro is associated with fatal outcome of
meningococcal disease . We investigated whether an
anti-inflammatory cytokine profile in the circulation is
associated with adverse outcome in other infectious
diseases . METHODS: We enrolled 464 consecutive patients
(272 men, 192 women) who presented to hospital with
fever (> or = 38.2 degrees C) . On admission we measured
plasma interleukin 10 (IL-10) and tumour necrosis factor
alpha (TNF alpha), and collected clinical and
microbiological data on the febrile illness, then
followed up all patients for clinical outcome .
FINDINGS: In at least 399 of the 464 patients fever was
caused by infection . 33 patients died after a median
hospital stay of 11 days (interquartile range 3-20) .
Concentrations of IL-10 were significantly higher in
non-survivors (median 169 pg/mL {IQR 83-530}) than in
survivors (median 88 pg/mL {42-235}, p=0.042) . When
dichotomised around the median, the mortality risk was
two times higher in patients who had high concentrations
of IL-10 than in those with low concentrations (relative
risk 2.39 {95% CI 1.07-5.33}), in patients with low and
high concentrations of TNF alpha . In the 406 patients
without haemodynamic deterioration in the first 24 h,
IL-10 was higher and TNF alpha lower in patients who
died than in those who survived . The ratio of IL-10 to
TNF alpha was higher in non-survivors (median 6.9
{3.0-21.0}) than in survivors (median 3.9 {2.0-7.0},
p=0.040) . This ratio was highest in patients who died
without underlying disease (median 21.5 {5.0-25.0}) .
Age, sex, and duration of fever before admission did not
explain the differences in IL-10 and TNF alpha .
INTERPRETATION: An anti-inflammatory cytokine profile of
a high ratio of IL-10 to TNF alpha is associated with
fatal outcome in febrile patients with
community-acquired infection . Our findings caution
against a widespread use of proinflammatory cytokine
inhibition in patients with sepsis.
J Clin Epidemiol, 1998 Sep, 51(9), 717 - 21
Outcome of pre-hospital antibiotic treatment of
meningococcal disease; Sorensen HT et al.; OBJECTIVE: To
assess the effect of pre-hospital antibiotic treatment
given by general practitioners to patients with
meningococcal disease . DESIGN: A 16-year
population-based historical follow-up study based on
referral letters and hospital records in the County of
North Jutland, Denmark . SUBJECTS: 320 patients with
meningococcal disease, of whom 302 were examined by a
general practitioner before admission to hospital . MAIN
OUTCOME MEASURES: Death . RESULTS: 44 patients (14.6%)
were given antibiotic treatment by the referring general
practitioner . Nine of these (20.5%) died, compared with
16 (6.2%) patients who did not receive pre-hospital
antibiotic treatment . The presence of skin bleeding,
petechiae, and impaired consciousness were strongly
associated with case fatality . Even after adjustment
for these variables the odds ratio (OR) for death in
patients treated with antibiotics was high (OR = 3.2;
95% CI, 0.9-10.6) . In the 15 patients with skin
bleeding (ecchymoses, suggillations) the case fatality
rate was 100% in patients treated with antibiotics, and
50% in patients who did not receive antibiotics before
hospitalization . If skin bleeding was replaced in the
models by the presence of disseminated intravascular
coagulation on admission, the OR for death in patients
with pre-hospital antibiotic treatment was 35.9 (95% CI,
2.9-441.8) in the presence of disseminated intravascular
coagulation and 1.9 (95% CI, 0.2-19.5) in its absence .
CONCLUSIONS: Pre-hospital treatment is mainly given to
the most severe cases with expected high case fatality,
and this confounding by indication was probably not
fully adjusted for with the available data . The results
contradict previous findings but provide reason to doubt
the benefit of pre-hospital antibiotic treatment in
patients with meningococcal disease.
Scand J Infect Dis, 1998, 30(2), 198 - 200
Pharyngolaryngitis caused by Neisseria meningitidis;
Mattila PS et al.; Neisseria meningitidis is a causative
agent of life-threatening cases of meningitis and
sepsis, but it can also cause mild and self-limiting
bacteraemia . Patients with N. meningitidis sepsis or
meningitis often describe signs of upper respiratory
tract infection before the onset of invasive disease.
Viral respiratory infections have been associated with
invasive meningococcal diseases and they may contribute
to these prodromal symptoms.
N . meningitidis can be
cultivated from the throats of asymptomatic carriers and
it likely enters the circulation through the upper
respiratory tract . However, it is unclear whether N .
meningitidis can cause simple pharyngitis . Here we
describe a case of acute fulminant pharyngolaryngitis
caused by N . meningitidis as verified by positive blood
cultures.
Scand J Infect Dis, 1998, 30(2), 196 - 8
Acute meningococcal epiglottitis and septicaemia in a
65-y-old man; Sivalingam P et al.; We report a case of
acute meningococcal epiglottitis in a 65-y-old man . He
was noted to have stridor of acute onset . We highlight
the importance of the diagnosis of acute epiglottitis,
early establishment of an airway and appropriate
antibiotic therapy . This case report mainly concerns
the association of unusual pathogen Neisseria
meningitidis and adult acute epiglottitis.
J Infect Dis, 1998 Sep, 178(3), 870 - 4
Induction of immunologic refractoriness in adults by
meningococcal C polysaccharide vaccination; Granoff DM
et al.; Thirty-four adults were vaccinated with 1/50 of
the usual dose of meningococcal polysaccharide vaccine
(1 microg of A, C, Y, and W135 polysaccharides, given
intramuscularly) . This dose was selected as a probe to
assess B cell memory . The probe elicited meningococcal
C bactericidal antibody responses in all 18 adults who
had been vaccinated 4 years earlier with an
investigational meningococcal A and C
oligosaccharide-protein conjugate vaccine and in the
majority of the 11 subjects vaccinated for the first
time . In contrast, the responses of the 5 adults given
a full dose of licensed polysaccharide vaccine 4 years
earlier were <1/10 of those of the other 2 groups .
Thus, adults previously given a full dose of
meningococcal polysaccharide vaccine show evidence of
immunologic refractoriness to group C polysaccharide,
whereas refractoriness is not observed after conjugate
vaccination . These findings have implications for the
use of meningococcal polysaccharide vaccine when the
risk of disease is low.
BMJ, 1998 Sep 5, 317(7159), 621 - 5
Which contacts of patients with meningococcal disease
carry the pathogenic strain of Neisseria meningitidis? A
population based study; Kristiansen BE et al.;
OBJECTIVES: To determine the prevalence of the
pathogenic strain of Neisseria meningitidis in contacts
of patients with meningococcal disease, and to determine
which contact groups are likely to be carriers and
warrant chemoprophylaxis . DESIGN: Population based
study . SETTING: Norwegian county of Telemark .
SUBJECTS: 1535 primary contacts of 48 patients with
meningococcal disease, and 78 secondary contacts .
INTERVENTIONS: Carriers of the pathogenic strain were
treated with rifampicin . All household members and
kissing contacts under 15 years of age were treated with
oral penicillin . Contacts were taught to recognise the
symptoms of meningococcal disease . RESULTS: In 27 of 48
cases investigated, contacts carrying the pathogenic
strain of N meningitidis were found . A total of 42 such
contacts were identified . Contacts were stratified into
three classes according to the assumed closeness of
contact with patients . In class 1 (household members
and kissing contacts) the prevalence of the pathogenic
strain was 12.4% (95% confidence interval 5.5% to 19.3%)
. In classes 2 and 3 the prevalence was 1.9% (0.9% to
3.4%) and 1.6% (0.14% to 3.1%) . CONCLUSIONS: There is a
high rate of carriage of the pathogenic strain of N
meningitidis in patients' household members and kissing
contacts, and this supports the practice of giving
chemoprophylaxis to these contacts . The prevalence of
carriage among other contacts is 2-3 times that found in
the general population (0.7%); the benefits of
chemoprophylaxis to these contacts may be marginal.
Commun Dis Public Health, 1998 Mar, 1(1), 54 - 6
Creating a national service for the diagnosis of
meningococcal disease by polymerase chain reaction;
Kaczmarski EB et al.; The widening gap observed between
numbers of culture confirmed and notified cases of
meningococcal infection has driven the development of
non-culture based polymerase chain reactions (PCRs) to
enhance the detection of meningococcal disease . The
development of a national PCR-based service increased
the number of laboratory confirmed cases of
meningococcal disease by 35% in the first year .
Advancing technology in the laboratory is reducing
in-lab processing time.
Nurse Pract, 1998 Aug, 23(8), 30, 33 - 6, 39-40 passim
Meningococcal disease: recognition, treatment, and
prevention; Herf C et al.; Meningococcal disease is an
infection caused by Neisseria meningitidis, a
gram-negative diplococcus that is the leading cause of
bacterial meningitis in children and young adults in the
United States, with an estimated 2,600 cases reported
each year . N . meningitidis infection rates are highest
in children 3 to 12 months of age . Four distinct
clinical situations are associated with meningococcal
infection . The most common is asymptomatic
nasopharyngeal colonization . Benign bacteremia is
discovered in the absence of classical clinical findings
of meningococcemia, but blood cultures are positive for
N . meningitidis . Meningitis, the most common
pathologic presentation, is associated with fever,
headache, and nuchal rigidity . The mortality rate is
about 5% in children and 10% to 15% in adults .
Meningococcemia, the most severe form of infection, may
involve petechial rash, hypotension, and disseminated
intravascular coagulation . It is a fulminant condition
that can, if untreated, progress from initial symptoms
to coma and death in 12 to 48 hours . Spread of these
endemic cases can be controlled by administering
prophylactic antibiotics to close contacts of patients.
Vaccine, 1998 Oct, 16(17), 1633 - 9
Effect of adjuvants in the isotypes and bactericidal
activity of antibodies against the transferrin-binding
proteins of Neisseria meningitidis; Gomez JA et al.;
Twenty-eight Neisseria meningitidis strains of different
serogroups, serotypes, and TbpB isotypes were used to
test the effect of five adjuvant formulations on the
immune response to the meningococcal transferrin-binding
proteins (Tbps) in mice . Levels of anti-Tbps antibodies
were relatively low when purified TbpA-TbpB complexes
were used for immunization, those obtained with the RAS
adjuvant being the highest, and the isotype distribution
reveals a prevalence of the non-bactericidal IgG1 .
Specific anti-Tbps antibody levels were five to 125
times higher immunizing with whole outer membrane
vesicles, with bactericidal isotypes prevailing, which
suggests that presentation of these antigens in their
natural conformation is crucial to elicit a good
response . Nevertheless, bactericidal activity did not
correlate with these characteristics, confirming that it
must be also influenced by other factors, and direct
evaluation of the killing ability is necessary to draw
conclusions about the efficacy of antigens or adjuvants
in vaccine design.
J Clin Immunol, 1998 Jul, 18(4), 272 - 82
Expression of properdin in complete and incomplete
deficiency: normal in vitro synthesis by monocytes in
two cases with properdin deficiency type II due to
distinct mutations; Fredrikson GN et al.; Three
properdin deficiency phenotypes have been
reported--complete deficiency (type I), incomplete
deficiency (type II), and dysfunction of properdin
protein (type III)--all associated with increased
susceptibility to meningococcal disease . Expression of
properdin by monocytes was examined in type I deficiency
and in two unrelated cases with type II deficiency, one
from a Swedish and one from a Danish family . The
properdin gene in the Danish family contained a point
mutation in exon 8 causing a Gln316-->Arg substitution,
distinct from a point mutation in exon 4 previously
found in the Swedish family . Both genes coded for
physicochemically abnormal properdin molecules with
changed hydrophilicity . Monocytes from all the
properdin-deficient individuals produced properdin mRNA
in a normal fashion . In type I deficiency no
intracellular or secreted properdin was found,
indicating rapid intracellular degradation . Monocytes
from the males with type II deficiency expressed and
secreted properdin normally . Properdin in sera with
type II deficiency showed abnormal oligomerization with
a relative decrease in properdin trimers and tetramers .
Our findings suggest that the low concentration of
circulating properdin in type II deficiency is caused by
increased extracellular catabolism . Analysis of
properdin expression by monocytes in a female carrier in
the family with properdin deficiency type I provided
direct evidence of lyonization at the cellular level.
J Burn Care Rehabil, 1998 Jul-Aug, 19(4), 324 - 9
Integra Artificial Skin as a useful adjunct in the
treatment of purpura fulminans; Besner GE et al.;
Purpura fulminans is a devastating disorder
characterized by rapidly progressing hemorrhagic
necrosis of the skin, vascular collapse, and
disseminated intravascular coagulation . It is most
often seen in children, and it is usually preceded by
meningococcemia or another infection . Most often, the
disorder results in severe skin loss, but it can also
result in the need for extremity amputations . In
extreme cases, wound coverage after excision may be
problematic because of the limited existence of donor
sites and the need for amputation revisions . The case
of a 21/2-year-old male requiring amputations of all
four extremities due to severe purpura fulminans is
presented to illustrate the use of Integra Artificial
Skin (Integra Lifesciences Corp., Plainsboro, NJ) to
obtain immediate wound closure . Integra Artificial Skin
is a bilayered skin substitute that engrafts to a viable
wound bed . In the case presented here, where the
viability of the underlying tissue of the amputated
stumps was questionable, the artificial skin acted as an
indicator of that viability . It engrafted well onto the
upper extremity stumps, which were of excellent
viability, but it needed to be replaced on the lower
extremity stumps, which required further debridement and
amputation revisions . The use of artificial skin spared
the patient the immediate use of his limited and
valuable autograft sites . In conclusion, Integra
Artificial Skin can be a useful adjunct in the treatment
of severe purpura fulminans that includes skin and
extremity necrosis.
Anaesthesia, 1998 Jun, 53(6), 580 - 3
Pneumopericardium: an unusual cause for cardiac arrest;
Djaiani G et al.; A 1-year-old boy breathing via a
T-piece system and recovering from meningococcal
septicaemia in the intensive care unit suffered a severe
bout of coughing and developed bilateral pneumothoraces
and tension pneumopericardium resulting in
electromechanical dissociation and asystole .
Conventional cardiopulmonary resuscitation and
adrenaline boluses were unsuccessful . Administration of
20 ml.kg-1 of colloid and 3 mmol.kg-1 of sodium
bicarbonate solutions produced instantaneous return of
cardiac, output . The deleterious effects of cardiac
tamponade appeared to decrease with increasing cardiac
filling pressures . The patient was managed
conservatively and he made a full recovery with no signs
of residual neurological deficit.
J Clin Microbiol, 1998 Sep, 36(9), 2623 - 8
Clonal distribution of invasive Neisseria meningitidis
isolates from the Norwegian county of Telemark, 1987 to
1995; Aakre RK et al.; Forty-two Neisseria meningitidis
isolates were obtained from patients with meningococcal
disease in the Norwegian county of Telemark (January
1987 to March 1995), and all were compared by PCR
amplicon restriction endonuclease analysis (PCR-AREA) of
the dhps gene, chromosomal DNA fingerprinting, and
serological analysis . PCR-AREA divided the isolates
into 11 classes, of which 4, comprising 15, 8, 6, and 2
isolates, were clonal while the remaining 8 classes were
genetically heterogeneous or contained only 1 isolate .
Three of the four clonal classes could be tentatively
equated with recognized epidemic clones (ET5, ET37, and
cluster A4) on the basis of their phenotypic
characteristics, while the remaining clone appears to be
new . There were significant differences in the
geographical distribution of clones, with class 1
(ET5-like) isolates significantly overrepresented in
rural parts of Telemark . Class 1 (ET5-like) isolates
occurred throughout the study period and were dominant
in 1987 . Class 2 (ET37-like) isolates occurred from
1988 to 1992, and class 3 isolates (with no recognizable
ET affinities) were found only in 1991 and 1992.
J Clin Microbiol, 1998 Sep, 36(9), 2465 - 70
Necessity of molecular techniques to distinguish
between Neisseria meningitidis strains isolated from
patients with meningococcal disease and from their
healthy contacts; Vogel U et al.; Serogroup C strains of
Neisseria meningitidis were isolated from a Germany
patient with severe meningococcal disease after a trip
to the Czech Republic . These strains (case isolates)
were characterized by classical and molecular
techniques, as were other strains (carrier isolates)
isolated from healthy contacts . Five of 10 carrier
isolates had switched off the expression of capsular
polysaccharide, as demonstrated by a serogroup-specific
PCR . The two case isolates were indistinguishable by
multilocus sequence typing and belonged to the ET-37
complex . The carrier isolates belonged to four
different sequence types, all unrelated to that of the
case strains . Pulsed-field gel electrophoresis showed
that the case isolates differed from reference ET-37
complex strains from the Czech Republic and Canada as
well as from all the carrier isolates . The isolate from
the patient's nasopharynx was indistinguishable from the
blood isolate except for a 40,000-bp chromosomal
deletion that had occurred during systemic spread.
Hum Genet, 1998 Jun, 102(6), 605 - 10
Nonsense mutation in exon 4 of human complement C9 gene
is the major cause of Japanese complement C9 deficiency;
Kira R et al.; Deficiency of the ninth component of
human complement (C9) is the most common complement
deficiency in Japan but is rare in other countries . We
studied the molecular basis of C9 deficiency in four
Japanese C9-deficient patients who had suffered from
meningococcal meningitis . Direct sequencing of
amplified C9 cDNA and DNA revealed a nonsense
substitution (CGA-->TGA) at codon 95 in exon 4 in the
four C9-deficient individuals . An allele-specific
polymerase chain reaction system designed to detect
exclusively only one of the normal and mutant alleles
indicated that all the four patients were homozygous for
the mutation in exon 4 and that the parents of patient 2
were heterozygous . The common mutation at codon 95 in
exon 4 might be responsible for most Japanese C9
deficiency.
Rev Saude Publica, 1998 Feb, 32(1), 89 - 97
{Meningococcal disease: epidemiology and control of
secondary cases}; Barroso DE et al.; Epidemiological
features of meningococcal disease described as from the
second half of the 80's inclusive, have motivated a
revision of current guidelines for sporadic disease and
outbreak control . The increase of disease among
teenagers and linked cases involving schools are the two
most significant aspects that have prompted the revision
of control measures . Vaccination routines and advice
for the disease management of clusters are also relevant
features recently revised . This present paper describes
the management and some epidemiological features of
secondary cases.
J Infect Dis, 1998 Aug, 178(2), 451 - 9
Dynamics of carriage of Neisseria meningitidis in a
group of military recruits: subtype stability and
specificity of the immune response following
colonization; Jones GR et al.; Meningococcal carriage
and the immune response to colonization were studied in
a group of military recruits undergoing basic training .
Subtyping by determination of the class 1 protein
sequence clearly differentiated between strains and
demonstrated the dynamics of carriage and transmission .
Expression of class 1 protein by each strain remained
stable during prolonged carriage by different subjects .
Following colonization, a marked increase in serum
bactericidal response occurred, which was specific for
the subtype of the acquired strain and was associated
with an increase in reactivity by Western blot to the
homologous class 1 protein . Subjects colonized by
multiple strains showed evidence of a specific immune
response to the class 1 protein of each strain acquired
. The subtype specificity of the bactericidal response
to meningococci and the stability of expression of the
class 1 protein have important implications for the
design of vaccines for prevention of serogroup B
meningococcal disease.
J Emerg Med, 1998 Jul-Aug, 16(4), 643 - 7
Rupert Waterhouse and Carl Friderichsen: adrenal
apoplexy; Varon J et al.; The Waterhouse-Friderichsen (WFS)
syndrome, also known as purpura fulminans, is described
as acute hemorrhagic necrosis of the adrenal glands and
is most often caused by meningococcal infection . This
clinical entity is more frequently seen in the pediatric
than the adult population and is associated with a high
morbidity and mortality . The initial presenting
complaints for patients with the WFS usually include a
diversity of nonspecific, vague symptoms such as cough,
dizziness, headache, sore throat, chills, rigors,
weakness, malaise, restlessness, apprehension, myalgias,
arthralgias, and fever . These symptoms are usually
abrupt in their onset . Petechiae are present in
approximately 50-60% of patients . The clinical
diagnosis of WFS may be relatively straightforward or
extremely challenging . Patients who appear in the
initial and nontoxic-appearing stage without any skin
lesions may be difficult to distinguish from a benign
viral illness . When a patient presents with fever and
petechiae, WFS must be considered, even when the patient
has a non-toxic appearance . Due to the rapid
progression and often devastating consequences, therapy
should be instituted as soon as the diagnosis is
suspected.
Biochem J, 1998 Aug 15, 334 ( Pt 1), 269 - 73
Transferrin-binding protein B isolated from Neisseria
meningitidis discriminates between apo and diferric
human transferrin; Boulton IC et al.; Neisseria
meningitidis utilization of human serum transferrin (hTF)-bound
iron is an important pathogenicity determinant . The
efficiency of this system would clearly be increased
through preferential binding of diferric hTF over the
iron-free form . To characterize this process,
functionally active meningococcal transferrin-binding
protein A (TbpA) and TbpB have been purified from N .
meningitidis using a novel purification procedure . The
association of isolated Tbps and Tbps in the presence of
hTF was investigated by gel filtration . Co-purified
TbpA+B formed a complex of molecular mass 300 kDa which
bound 1-2 molecules of hTF . Purified TbpA formed a
complex of 200 kDa, indicating association as a dimer,
whereas TbpB aggregated to form multimers of variable
sizes . On recombining TbpA and TbpB, a stable complex
of equivalent size to co-purified TbpA+B was formed .
This complex may be composed of a single TbpA dimer and
1 molecule of TbpB . The technique of surface plasmon
resonance (SPR) was used to demonstrate clearly that
TbpB of either high (85 kDa) or low (68 kDa)
molecular-mass preferentially bound diferric hTF in
comparison with iron-free hTF . This selectivity was not
observed with TbpA, but was found at low levels with
co-purified TbpA+B . Individual TbpA and TbpB,
recombined in a 1:1 molecular ratio, showed
iron-mediated discriminatory binding at an intermediate
level . SPR was also used to show that TbpA and TbpB
bound to distinct regions of hTF, and that prior
saturation with TbpB reduced subsequent TbpA binding .
The results demonstrated that hTF bound more TbpA than
TbpB, with an approximate ratio of 2:1 . We have
demonstrated that in vitro, TbpA+B exists as a receptor
complex composed of a TbpA dimer and one molecule of
TbpB, and that TbpB selectively binds diferric hTF . We
propose that, in vivo, TbpA and TbpB also exist as a
receptor complex, with TbpB selectively binding diferric
hTF, bringing it close to TbpA, the transmembrane
component, where the ferric iron can be transported to
the periplasm.
Epidemiol Infect, 1998 Jun, 120(3), 263 - 70
A cluster of meningococcal disease in western Sydney,
Australia initially associated with a nightclub; Jelfs J
et al.; Fourteen cases of meningococcal disease (MD)
occurred in August September 1996 in western Sydney,
Australia . Seven of the 10 young adults affected had a
direct or indirect link with a local nightclub . Ten of
11 systemic meningococcal isolates had the phenotype
C:2a:P1.5 and showed close genetic relationship by
pulsed-field gel electrophoresis (PFGE) . Organisms of
this phenotype have not previously caused outbreaks in
Australia, but have been associated with outbreaks and
hyperendemic serogroup C MD in Europe, Canada, and the
United States . This is the largest cluster of serogroup
C MD reported in urban Australia, and the first
involving a nightclub . The strain differentiation
results were available rapidly enough to augment
epidemiological investigations on a daily basis . Public
health staff could thus establish links between cases
quickly, follow the spread of new cases in the
community, give accurate information to health officials
and the press, and utilize existing knowledge about the
characteristics of this phenotype to predict likely
developments during the outbreak and afterwards . The
strain differentiation data was also very helpful when
the role of vaccination was considered, and existing
guidelines on the management of outbreaks of MD could be
used effectively for the first time in western Sydney.
Epidemiol Infect, 1998 Jun, 120(3), 257 - 62
Amplification of the meningococcal porB gene for
non-culture serotype characterization; Urwin R et al.;
Since 1992, the proportion of culture-confirmed
meningococcal infections compared with numbers of
notified cases of meningococcal disease has decreased in
England and Wales . As most meningococcal strain
characterization methods depend on a clinical isolate,
this has resulted in a loss of epidemiological
information . To address this problem, and to aid
nonculture diagnosis, a semi-nested PCR protocol for the
amplification of the meningococcal porB gene from
clinical specimens was developed . This gene encodes the
meningococcal serotyping antigen; strain typing data was
provided by hybridization of allele-specific
oligonucleotide probes to the digoxigenin-labelled porB
amplicon in a 'PCR ELISA' . This assay was specific for
meningococcal DNA and sensitivities of 0.81 for
cerebrospinal fluid (CSF), 0.57 for serum, and 0.62 for
whole blood taken from patients with proven
meningococcal infection were obtained.
Sante, 1998 May-Jun, 8(3), 245 - 8
{Optimizing the response to epidemics of meningococcal
meningitis: report of a workshop of experts at CERMES
(Niamey, Niger, 12th to 14th January 1998)}; Chippaux JP
et al.; Recent meningitis epidemics in West Africa have
drawn attention to shortcomings in the response of the
health services . The health ministries of the countries
involved have identified particular requirements .
Following WHO recommendations, OCCGE organized a meeting
of experts at CERMES, Niamey, in January 1998 . The aim
of this workshop was to consider the problems common to
these countries, identify their needs and to produce
concrete recommendations defining the roles of OCCGE and
CERMES . Difficulties in mobilization, as no procedure
had been established, and a lack of resources limited
the efficiency of the response to epidemics . There was
also insufficient training of personnel and laboratory
facilities were often inadequate . OCCGE could draft a
procedure manual specifying tasks and responsibilities
for the control of an epidemic . It was suggested that a
sub-regional stock of drugs, vaccines and injection
equipment should be set up at CERMES . This should
improve the speed of the response and complement
national and international distribution systems . The
group stressed the importance of improving the
surveillance of meningitis epidemics . This approach
depends on a structured network based around a reference
laboratory . CERMES plans to support government
initiatives by training and by maintaining the network .
Efforts will be made to report and make best use of
epidemiological information at all levels of the "health
pyramid" . Some OCCGE institutes (e.g . IPR and CERMES)
have computer tools such as the Geographical Information
System, which can be made available to governments .
Analysis of sub-regional epidemics demonstrated the
limitations of an alert threshold of 15 cases per
100,000 people . The sensitivity and specificity of this
threshold differs between climatic zones OCCGE
recommends that each country carry out its own research
to determine the most appropriate alert threshold for
each zone . Epidemics are currently managed by treatment
with short courses of chloramphenicol in oil (injected
into muscle) . This approach may change as ceftriaxone
becomes more affordable . The systematic use of
ceftriaxone in infants under the age of 1 year
presenting with meningitis is justified by the frequency
of non-meningococcal bacterial causes . A consensus was
reached on the most appropriate vaccination strategies:
Emergency vaccination implemented rapidly in response to
an epidemic . The entire population of a district
between the age of 6 months and 30 years are vaccinated
. Prophylactic vaccination in high-risk zones . This is
carried out in the zone itself or in neighboring regions
where there was an epidemic the preceding year . There
is evidence that those not infected during an epidemic
are at high risk the following year . These vaccinations
should be carried out as soon as possible, at least
before the start of the next epidemic season .
Systematic vaccination is currently limited to special
groups (e.g . school children, military personnel and
pilgrims) . It is hoped that the conjugated vaccine will
become available for integration into the infant
vaccination program.
Rev Cubana Med Trop, 1997, 49(3), 196 - 203
{Adverse reactions and immune response to
Heberbiovac-HB vaccine administered to infants
simultaneously with DPT and VA-MENGOC-BC}; Diaz Gonzalez
M et al.; The Cuban recombinant yeast-derived hepatitis
B vaccine (Heberbiovac-HB) was administered to 2 groups
of infants aged 3 months . A dosage of 10 micrograms was
used through a scheme of 0, 1 and 6 and 0, 1, 2 and 12,
coinciding with the DPT and anti-meningococcal vaccines,
according to the immunization schedule . Reactogenicity
and immunogenicity were studied in both groups . The
reactions observed were mild and similar to other
studies, where fever , erythema and induration were the
most common signs . These 2 groups had high percentages
of children with titres of antibodies anti HBs above 100
UI/L-1 . It is demonstrated the acceptable
reactogenicity of the vaccine and the non-immunological
interference of other vaccines.
Intensive Care Med, 1998 Jun, 24(6), 616 - 9
Combined lung injury, meningitis and cerebral edema:
how permissive can hypercapnia be?
Tasker RC, Peters MJ.
We describe a patient with combined meningococcal
septicemia and meningitis, cerebral edema and acute
respiratory distress syndrome, in whom we balanced the
conflicting carbon dioxide strategies for optimal
pulmonary and neurological management using jugular
oxygen saturation (SjvO2) monitoring to identify the
upper limit of "tolerable" hypercapnia . Our
observations suggest that significant acidosis was not
well tolerated; however, cautious induction of pH down
to 7.32 and an arterial carbon dioxide tension (PaCO2) <
5.9 kPa was tolerated acutely without significant
cerebral hyperemia . Moreover, with the development of
metabolic compensation and normal pH, higher levels of
PaCO2 could be permitted . In similar cerebro-pulmonary
circumstances we suggest that these findings warrant
consideration . Alternatively, invasive monitoring of
SjvO2 could be undertaken so that patient-specific
criteria for permissive hypercapnia can be determined.
J Accid Emerg Med, 1998 Jul, 15(4), 249 - 51
Prospective study of "door to needle time" in
meningococcal disease; Riordan FA et al.; OBJECTIVE: To
measure the promptness of antibiotic treatment in
children with meningococcal disease . METHODS: "Door to
needle time" for parenteral antibiotics in children with
meningococcal disease was recorded prospectively as part
of a larger study . The time from arrival at hospital
until the first dose of parenteral antibiotics was
recorded in 100 children with meningococcal disease
(median (range) age 21 (3-168) months) admitted to four
Merseyside hospitals . RESULTS: Forty five children
presented directly to the accident and emergency (A&E)
department . Parenteral penicillin was given before
admission to 19 of the 55 children referred by general
practitioners (GPs) . Median door to needle time was 36
minutes . All children with a typical petechial rash on
arrival received antibiotics within 60 minutes .
Antibiotics were given sooner to those with severe
disease (p = 0.01) and later to those without a rash (p
= 0.007) . CONCLUSIONS: The first dose of parenteral
antibiotics for most children with meningococcal disease
was given in A&E . When awareness of meningococcal
disease is heightened by ongoing research, those with a
petechial rash are treated within 60 minutes .
Strategies to improve immediate treatment of
meningococcal disease should include education of A&E
staff as well as GPs.
Mol Microbiol, 1998 Jun, 28(6), 1153 - 63
Pilus-mediated adhesion of Neisseria meningitidis: the
essential role of cell contact-dependent transcriptional
upregulation of the PilC1 protein; Taha MK et al.; Pilus-mediated
adherence makes an essential contribution to the
pathogenesis of Neisseria meningitidis by allowing the
initial localized adherence . Pili are assembled from a
protein subunit called pilin . Two proteins, PilC1 and
PilC2, are also key elements in the formation of pili as
the production of at least one PilC protein is required
for pilus assembly . In addition, PilC1 but not PilC2
modulates adhesiveness, most probably by being the
adhesin . Recently, both genes have been demonstrated to
be controlled by different promoters, pilC2 is expressed
from a single transcription starting point (TSP),
whereas pilC1 has three TSPs . One of these, PC1.1,
corresponds to the unique TSP of pilC2, and two others,
PC1.2 and PC1.3, are located in a region upstream of
pilC1 but not pilC2 . This suggests that both genes may
be under the control of separate regulatory pathways .
In this work, by engineering pilC1-lacZ and pilC2-lacZ
transcriptional fusions, we provide evidence that
expression of pilC1, but not that of pilC2, is
transiently induced by bacterial cell contact . This
induction required viable cells, did not need the
presence of pili and relied on the expression of pilC1
from PC1.3 . Destruction of this TSP by site-directed
mutagenesis did not significantly diminish the piliation
level or the basal expression of PilC1, but led to the
loss of cell contact-dependent upregulation of pilC1 and
to a dramatic decrease in bacterial adhesiveness . Taken
together, these data demonstrate that cell
contact-dependent upregulation of the transcription of
pilC1 at PC1.3 is essential for meningococcal pilus-mediated
adhesion.
Ugeskr Laeger, 1998 Jul 13, 160(29), 4325 - 6
{Parvovirus B19 infection--a meningococcus-like
sepsis}; Frederiksen EH et al.; Two otherwise healthy
adults with fever and haemorrhagic exanthema are
described . In both, primary human parvovirus infection
was diagnosed . The clinical picture of fever and
haemorrhagic exanthema should always arouse suspicion of
serious disease such as meningococcal infection . If the
patient is unaffected, however, primary human parvovirus
infection should be borne in mind.
Burns, 1998 May, 24(3), 272 - 4
Surgical treatment of extensive skin necrosis secondary
to purpura fulminans in a patient with meningococcal
sepsis; Arevalo JM et al.; Meningococcal sepsis is
associated with a high mortality rate . These patients
may show severe disseminated intravascular coagulation (DIC)
and skin necrosis . There is very little published
experience regarding the surgical treatment of this
complication . The similarity between skin necrosis
secondary to DIC and full thickness cutaneous burns
provides the rationale for its treatment as if it was a
deep burn . We report the surgical treatment of
extensive skin necrosis in a patient with meningococcal
sepsis and DIC . This treatment is similar to that used
in full thickness burns, including excision of necrotic
tissue and coverage with autografts, as well as
amputation of extremities if distal coverage is not
possible.
Carbohydr Res, 1998 Feb, 307(3-4), 311 - 24
The lipooligosaccharide (LOS) of Neisseria meningitidis
serogroup B strain NMB contains L2, L3, and novel
oligosaccharides, and lacks the lipid-A 4'-phosphate
substituent; Rahman MM et al.; The complete structure of
the lipooligosaccharide (LOS) from Neisseria
meningitidis strain NMB (serotype 2b:P1.2,5), a
serogroup B cerebrospinal fluid isolate, was
determined.Two oligosaccharide (OS) fractions and
lipid-A were obtained following mild acid hydrolysis of
the LOS . The structures in these fractions were
determined using glycosyl composition and linkage
analyses, N spectroscopy and mass spectrometry . One
oligosaccharide fraction (OS1) consists of a molecule
having a glycosyl sequence identical to that previously
reported for the LOS from immunotype L2 N . meningitidis
{A . Gamain, M . Beurret, F . Michon, J.-R . Brisson,
and H.J . Jennings, J . Biol . Chem.,267,(112) 922-925}
i.e., a lacto-N-neotetraose is attached to heptose I
(Hep I), with terminally linked N-acetylglucosaminosyl
and glucosyl residues attached to Hep II of the inner
core . Approximately 70% of this structure is acetylated
at O-6 of the terminally linked alpha-N-acetyl-glucosaminosyl
residue . As with the L2 structure, the NMB LOS
contained phosphoethanolamine (PEA) at O-6 or O-7 of the
Hep II residue . The second oligosaccharide fraction
(OS2) contains a a mixture of three different molecules,
all of which vary from one another in their glycosyl
substitution patterns of the Hep II residue . The most
abundant molecule in OS2 has a structure identical to
that of OSI, i.e., it has the L2 glycosyl sequence . A
second molecule (OS2a) lacks the terminal glucosyl
residue at O-3 of Hep II; i.e., it has a glycosyl
sequence identical to that of the mild acid released
oligosaccharide of N . meningitidis immunotype L3, L4,
or L7 LOSs . The third molecule (OS2b) is a novel
structure that lacks the terminal N-acetylglucosaminosyl
residue linked to O-2 of Hep II . Overall, 76% of OS
released from NMB LOS has the L2 structure, 15% is OS2a
(L3), and 9% is OS2b . A portion (20%) of the molecules
in the NMB LOS preparation also contained terminally
linked sialic acid attached to O-3 of the lacto-N-neotetraose
galactosyl residue, which is also consistent with the
L3, or L4 LOS structures . In contrast to the previously
reported structure of N . meningitidis lipid-A {V . A .
Kulshin, U . Zahringer, B . Linder, C.E . Frasch, C-M .
Tsai, B.A . Dmitriev, and E.T Rietschel, J . Bacteriol.,
174, (1992)1793-1800}, only 30% of the lipid-A from NMB
LOS possesses 4'-phosphate . Comparison with the lipid-A
of LOS purified from an isogenic acapsulate mutant, M7,
revealed that the 4'-position was almost completely
occupied with phosphate . These data emphasize the
structural heterogeneity of the OS and phosphate
substituents of Hep II, and 4'-phosphorylation of
lipid-A of meningococcal LOS.
APMIS, 1998 May, 106(5), 505 - 25
Population genetics and molecular epidemiology of
Neisseria meningitidis; Caugant DA; Under non-epidemic
conditions, Neisseria meningitidis causes disease
primarily in children under the age of 5 and the cases
are sporadic without any evident relationship between
them . Occasionally, localized outbreaks of
meningococcal disease occur, and sometimes epidemic
waves of disease may spread to several countries or even
continents and constitute a pandemic . In the past 10
years or so, population genetic analyses have provided
insights into the biology of the bacterium and the
epidemiology of meningococcal disease, improving our
understanding of the cause of epidemics . Through the
application of molecular methods, and especially
multilocus enzyme electrophoresis, to N . meningitidis
strains of worldwide origin, it has been possible to
identify virulent clones and provide a surveillance
system to warn of meningococcal epidemics . The
characteristics of the predominant clones which are
nowadays causing meningococcal disease in the world are
summarized here and the importance of population
genetics in interpreting the epidemiological data is
illustrated.
Lik Sprava, 1998 Mar-Apr, (2), 118 - 21
{The clinical use of Amoxiclav in patients with
suppurative meningoencephalitis}; Kononenko VV et al.;
Clinical use of Amoxiclav showed high therapeutic
efficacy in patients with purulent meningoencephalitis
both alone and in combination with cefalosporinum of the
first generation . Against the background of treatment
of patients with overt manifestations of
meningoencephalitis and neurotoxicosis meningeal and
encephalitic manifestations got attenuated during the
first week, with liquorodynamics being stabilized,
cerebrospinal fluid ameliorating by day 8-10 of the
disease course . Bacteriologic assays showed that up to
83.4% of bacterial flora most common in Ukraine are
sensitive to Amoxiclav, with such pathogenic organisms
as Pneumococcus, Meningococcus, hemophilia bacillus that
are actually main pathogens implicated in acute
meningoencephalitis in Ukraine being sensitive to the
above drug preparation in 100% of cases.
Scand J Infect Dis, 1998, 30(1), 69 - 75
Epidemiological markers in Neisseria meningitidis: an
estimate of the performance of genotyping vs phenotyping;
Weis N et al.; In order to estimate the performance of
genotypic vs phenotypic characterization of Neisseria
meningitidis, 2 methods, DNA fingerprinting and
multilocus enzyme electrophoresis (MEE), were assessed
as regards applicability, reproducibility and
discriminating capacity . 50 serogroup B and 52
serogroup C Neisseria meningitidis strains from 96
patients with meningococcal disease and 22 serogroup C
strains from healthy carriers were investigated . Both
methods were 100% applicable to meningococcal strains
and results of DNA fingerprinting as well as of MEE were
reproducible . The number of types defined by DNA
fingerprinting and MEE as compared to that defined by
phenotypic characteristics (serogroup, serotype,
serosubtype and sulphonamide resistance) was as follows:
for serogroup B strains from patients, 11 and 12 vs 8;
for serogroup C strains from patients, 10 and 15 vs 8;
and for serogroup C carrier strains, 12 and 19 genotypes
vs 10 phenotypes were defined . By use of both DNA
fingerprinting and MEE the number of genotypes defined
for the 3 groups of strains was 14, 17 and 19,
respectively . DNA fingerprinting and MEE showed a
discriminating capacity superior to that of phenotyping,
and as applied in the study MEE was superior to DNA
fingerprinting . Clusters of invasive strains were
reliably identified by phenotyping alone, whereas
determination of identity of carrier strains and an
invasive strain required genotyping.
ASDC J Dent Child, 1998 May-Jun, 65(3), 191 - 3
Meningococcal septicemia and disseminated intravascular
coagulation affecting the premaxillary permanent tooth
germs; Walton AG et al.; The following case describes
the dental effects resulting from a case of
meningococcal septicemia which caused a disseminated
intravascular coagulation and premaxillary osteomyelitis
at age two years . The effects went unnoticed for eight
years when delayed development of the maxillary incisors
was noted . Treatment involved surgical removal of the
dental remnants and provision of a removable partial
denture . Implants and ridge augmentation will be
considered in early adulthood.
Br J Gen Pract, 1998 Apr, 48(429), 1167 - 71
Recognizing meningococcal disease: the case for further
research in primary care; Granier S et al.; Most studies
describing the clinical presentation of meningococcal
disease use data derived from hospital-based studies .
This paper reviews current knowledge on the presentation
of meningococcal disease from a primary care perspective
. In a small proportion of cases with classical
features, making the diagnosis may be relatively simple
. In many cases, however, the general practitioner (GP)
is faced with the difficulty of discriminating between
the rare patient with life-threatening illness and the
vast majority who present with similar symptoms
secondary to self-limiting viral illness . In the
absence of reliable means of excluding the disease, GPs
will need to consider the possibility of meningococcal
disease in all ill and febrile patients in whom no cause
is apparent . Planned follow-up and clearer explanation
to patients may increase the chance of identifying
earlier those cases that evolve with time . More
research is required to identify key clinical and
contextual features that help GPs to predict or exclude
serious disease, and to describe how this information is
used in decision-making . A framework for
conceptualizing the problems of researching illness is
provided, which takes into account the many factors that
influence clinical practice in primary care.
J Clin Microbiol, 1998 Aug, 36(8), 2342 - 5
Characterization of Neisseria meningitidis strains
causing disease in complement-deficient and
complement-sufficient patients; Fijen CA et al.;
Serotyping and serosubtyping of meningococci showed no
difference between isolates from 44 complement-deficient
persons and from 50 complement-sufficient persons with
meningococcal disease . Multilocus enzyme
electrophoretic typing of the meningococci revealed 54
electrophoretic types that were equally distributed
among isolates from complement-deficient and
complement-sufficient patients . Analysis of strains
isolated from eight complement-deficient persons with 11
recurrences of meningococcal disease showed that one
strain was identical to the strain previously isolated
from the same individual . Our results indicate that
there are no differences between the clonal
distributions of strains infecting complement-deficient
and complement-sufficient patients . Most recurrences
were infections caused by different strains.
J Clin Microbiol, 1998 Aug, 36(8), 2205 - 9
Diagnosis of meningococcal meningitis by broad-range
bacterial PCR with cerebrospinal fluid; Kotilainen P et
al.; We used broad-range bacterial PCR combined with DNA
sequencing to examine prospectively cerebrospinal fluid
(CSF) samples from patients with suspected meningitis .
Fifty-six CSF samples from 46 patients were studied
during the year 1995 . Genes coding for bacterial 16S
and/or 23S rRNA genes could be amplified from the CSF
samples from five patients with a clinical picture
consistent with acute bacterial meningitis . For these
patients, the sequenced PCR product shared 98.3 to 100%
homology with the Neisseria meningitidis sequence . For
one patient, the diagnosis was initially made by PCR
alone . Of the remaining 51 CSF samples, for 50 (98.0%)
samples the negative PCR findings were in accordance
with the negative findings by bacterial culture and Gram
staining, as well as with the eventual clinical
diagnosis for the patient . However, the PCR test failed
to detect the bacterial rRNA gene in one CSF sample, the
culture of which yielded Listeria monocytogenes . These
results invite new research efforts to be focused on the
application of PCR with broad-range bacterial primers to
improve the etiologic diagnosis of bacterial meningitis
. In a clinical setting, Gram staining and bacterial
culture still remain the cornerstones of diagnosis.
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