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Corruzione
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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
Med Sci Law, 1998 Jan, 38(1), 52 - 6
Digoxin-like immunoreactivity in early infantile death;
Couper RT et al.; The aim of this study was to determine
if the level of digoxin-like immunoreactivity in
post-mortem sera obtained from infants differs according
to the cause of death and if the level is related to
age, post-mortem interval, cardiac pathology or adrenal
weight . Twelve infants whose deaths were attributed to
sudden infant death syndrome (SIDS), and 11 infants who
died from other causes, had blood sampled between 3 to
53 hours post-mortem from their right atrial cavity .
Digoxin-like immunoreactivity was measured, using a
specific and sensitive digoxin radioimmunoassay, and was
detected in 7 of the infants who died of SIDS and 7 of
those who died from other causes . The highest levels
were seen in two patients who died from meningococcal
sepsis and haemorrhage, hyperpyrexia and encephalopathy
syndrome, respectively .
No correlation was detected
between the digoxin-like immunoreactivity level, gender,
age at death, post-mortem interval or cardiac pathology
. Digoxin-like immunoreactivity levels correlated with
adrenal weight . It is concluded that digoxin-like
immunoreactivity is frequently found in infant sera, but
levels are not specific to and are no higher in SIDS
infants than infants dying of other conditions.
Immunol Res, 1998, 17(1-2), 95 - 108
Peptide mimotopes of carbohydrate antigens; Kieber-Emmons
T; Carbohydrate structures have been identified as
significant antigens for bacterial, viral, and fungal
pathogens as well as targets on human tumor cells . Many
of these antigens are poorly immunogenic in humans,
requiring extensive adjuvant sublimation . Although
conjugate carbohydrate vaccines appear promising, there
are limitations of using carbohydrate formulations . An
alternative approach is to use surrogate antigens for
some carbohydrates . We are developing peptides that
mimic carbohydrates which might be further manipulated
to induce responses that target biologically important
carbohydrates expressed on pathogens and on tumor cells
. We have shown that peptide mimotopes of carbohydrates
induce immune responses to carbohydrate structures with
in vivo and vitro functionality . Model systems include
the Neisseria group C meningococcal polysaccharide; the
histo-blood group-related antigens expressed on tumor
cells; and mannose, sialyl, and histo-blood
group-related carbohydrate epitopes expressed on human
immunodeficiency virus.
World Health Stat Q, 1997, 50(3-4), 170 - 7
Meningococcal disease: public health burden and control;
Tikhomirov E et al.; Meningococcal disease which is
increasing globally is still associated with a high
mortality and persistent neurological defects,
particularly among infants and young children . Sporadic
meningococcal meningitis occurs throughout the world,
with seasonal variations, and accounts for 10-40% of
endemic bacterial meningitis . Epidemic meningitis
occurs in any part of the world but the largest and most
frequently recurring epidemics have been in the
semi-arid area of sub-Saharan Africa where the current
pandemic is associated with attack rates exceeding 500
per 100,000 population and thousands of deaths . In the
Americas and Europe serogroup B is the predominant agent
causing systemic disease, followed in frequency by
serogroup C . Serogroup A meningococcus was historically
the main cause of epidemic meningococcal disease
globally and still predominates in Africa and Asia . A
range of internal and external factors predispose for
epidemics such as strain virulence, carriers, humoral
immunity, co-infections, low humidity and drought,
population movements and crowding . To respond to the
current situation and the expected spread of the
disease, WHO, in collaboration with its Member States
and various governmental and non-governmental agencies,
has developed a sustainable plan of action for
preparedness and control of meningitis.
Int J Cardiol, 1997 Dec 19, 62(3), 277 - 8
Asymptomatic temporary atrioventricular dissociation
complicating meningococcal meningitis; Shapira MY et
al.; We present a case of a young man with meningococcal
meningitis and various asymptomatic temporary ECG
abnormalities, including sinus bradycardia,
atrioventricular dissociation and non specific ST-T
changes.
Immunopharmacology, 1997 Dec, 38(1-2), 93 - 9
The effect of mannan-binding lectin on
opsonophagocytosis of Neisseria meningitidis;
Drogari-Apiranthitou M et al.; Mannan-binding lectin (MBL),
an acute phase protein with a structure and a function
very similar to that of C1q, is known to act as an
opsonin binding to a number of microorganisms . In order
to investigate the effect of MBL on the phagocytic
killing of meningococci, a serogroup B meningococcal
strain (H44/76) and its unencapsulated variant v24, as
well as a serogroup A meningococcal strain were
opsonized with MBL (purified from normal human plasma at
the State Serum Institute, Denmark) and used in a
phagocytic killing assay at a density of 7 x 10(3) CFU/ml
. Polymorphonuclear cells (PMNs) from one healthy donor
were isolated by density gradient centrifugation over
Percoll and added to the system (7 x 10(6) cells/ml) .
In a first set of experiments without addition of serum
or complement, no influence of MBL was observed on the
killing of any of these strains . Addition of MBL to
non-opsonized bacteria of the serogroup A strain did not
result in enhanced killing either; on the contrary, the
growth of this strain increased significantly when a
high MBL concentration (40 micrograms/ml) was used in
the presence of PMNs . Further investigations were
performed using sera of five individuals with late
complement component deficiency (LCCD) and a concomitant
MBL deficiency, vaccinated with a tetra-valent (ACYW135)
meningococcal capsular polysaccharide vaccine . Pre- and
post-vaccination sera (50% final concentration) were
tested against a group A strain opsonized or not with
MBL . In only one patient was there a moderate increase
of killing of the opsonized bacteria after vaccination
compared to pre-vaccination serum . Our results suggest
that MBL may not play a significant role in the
opsonophagocytosis of meningococci, irrespective of its
binding to unencapsulated and serogroup A strains.
Clin Exp Immunol, 1998 Jan, 111(1), 97 - 101
Meningococcal disease and polymorphism of FcgammaRIIa
(CD32) in late complement component-deficient
individuals; Platonov AE et al.; Late complement
component-deficient (LCCD) individuals lack plasma
bactericidal activity and are highly susceptible to
meningococcal disease . Phagocytosis plays a significant
role in immune defence against meningococci and involves
FcgammaRIIa (CD32) on leucocytes . Two allotypic forms
are currently recognized: FcgammaRIIa-R131 and RIIa-H131
. Neutrophils with the IIa-H/H131 allotype are more
effective in phagocytosis than IIa-R/R131 . We studied
the distributions of IIa-R131 and IIa-H131 allotypes
among 29 Russian LCCD patients who had suffered from
recurrent episodes of meningococcal disease . The
distribution of IIa-R/R131 to heterozygous IIa-R/H131 to
homozygous IIa-H/H131 genotypes was 0.14:0.29:0.57 for
LCCD patients who developed the first episode of disease
before 10 years of age . The distribution was
0.21:0.64:0.14 for patients who experienced
meningococcal disease above the age of 10 years (chi2 =
6, P < 0.05, odds ratio for IIa H/H131 versus R/R131 =
8) . Meningococcal disease had a 'grave' course in 14 of
31 disease episodes in patients with IIa-R/R131 and IIa-R/H131
allotypes, in contrast to 1 of 18 episodes in patients
with IIa-H/H131 allotype (chi2 = 7, P < 0.01, odds ratio
= 14) . We conclude that IIa-H/H131 individuals appear
to have a higher acquired antibody-mediated phagocytosis-dependent
resistance to meningococcal disease above the age of 10
years . Additionally, effective CD32-mediated
phagocytosis may restrict the severity of meningococcal
disease in LCCD patients with IIa-H/H131 phenotype.
Clin Exp Immunol, 1998 Jan, 111(1), 91 - 6
Molecular defects leading to human complement component
C6 deficiency in an African-American family; Zhu ZB et
al.; Complement component C6 deficiency (C6D) was
diagnosed in a 16-year-old African-American male with
meningococcal meningitis . The patient's father and two
brothers also had C6D, but gave no history of meningitis
or other neisserial infection . By using exon-specific
polymerase chain reaction (PCR)/single-strand
conformation polymorphism as a screening step and
nucleotide sequencing of target exons, we determined
that the proband was a compound heterozygote for two C6
gene mutations . The first, 1195delC located in exon 7,
is a novel mutation, while the second, 1936delG in exon
12, has been described before to cause C6D in an
unrelated African-American individual . Both mutations
result in premature termination codons and C6 null
alleles . Allele-specific PCR indicated that the
proband's two brothers also inherited the 1195delC
mutation from their heterozygous mother and the 1936delG
mutation from their homozygous father.
BMJ, 1998 Jan 24, 316(7127), 276 - 9
Recognising meningococcal disease in primary care:
qualitative study of how general practitioners process
clinical and contextual information; Granier S et al.;
OBJECTIVES: To describe the presentation of
meningococcal disease in primary care; to explore how
general practitioners process clinical and contextual
information in children with meningococcal disease; and
to describe how this information affects management .
DESIGN: Qualitative analysis of semistructured
interviews . SETTING: General practices in South
Glamorgan . SUBJECTS: 26 general practitioners who
between January 1994 and December 1996 admitted 31
children (under 16 years of age) in whom meningococcal
disease was diagnosed . MAIN OUTCOME MEASURES:
Categories of clinical rules and techniques used by
general practitioners in processing each case . RESULTS:
22 children had rashes; in 16 of them the rashes were
non-blanching . When present, a haemorrhagic rash was
the most important factor in the doctor's decision to
admit a child . 22 children had clinical features not
normally expected in children with acute self limiting
illnesses--for example, lethargy, poor eye contact,
altered mental states, pallor with a high temperature,
and an abnormal cry . Contextual information, such as
knowledge of parents' consultation patterns and their
normal degree of anxiety, played an important part in
the management decisions in 15 cases . Use of penicillin
was associated with the certainty of diagnosis and the
presence and type of haemorrhagic rash . CONCLUSION: The
key clinical feature of meningococcal disease--a
haemorrhagic rash--was present in only half of the study
children . The general practitioners specifically hunted
for the rash in some ill children, but doctors should
not be deterred from diagnosing meningococcal disease
and starting antibiotic treatment if the child is
otherwise well, if the rash has an unusual or scanty
distribution, or if the rash is non-haemorrhagic.
Epidemiol Mikrobiol Imunol, 1997 Dec, 46(4), 145 - 8
{Changes in clinical and epidemiologic characteristics
in Western Bohemia of invasive meningococcal disease
associated with the occurrence of an invasive clone of
Neisseria meningitidis}; Struncova V et al.; The authors
analyzed the incidence of meningococcal diseases in the
West Bohemian region in 1982-1996 . The draw attention
to changes of clinical and epidemiological
characteristics of the disease which appeared in 1994 in
conjunction with a new invasive clonus of Neisseria
meningitidis C:2a:P1.2, P1.5, ET-15/37 . While in
1982-1993 invasive meningococcal diseases had in 75% the
course of meningitis with a relatively low fatality
(4%), during the subsequent period a marked change
occurred . Since 1994 the disease took in the West
Bohemian region in 58% the course of sepsis with a
fatality of 16% . 25% cases of meningococcal meningitis
were diagnosed combined sepsis and meningitis in 17% .
The disease lost its seasonal character and the authors
confirmed the highest incidence of the disease in the
age group from 15-19 years and 0-4 years . Neisseria
meningitidis group C was detected in 1994-1996 in 73%
and the invasive clone C:2a:P1.2, P1.5, ET-15/37 in 62%.
Microbiology, 1998 Jan, 144 ( Pt 1), 157 - 66
Recombinational reassortment among opa genes from ET-37
complex Neisseria meningitidis isolates of diverse
geographical origins; Hobbs MM et al.; Opacity (Opa)
proteins are a family of antigenically variable
outer-membrane proteins of Neisseria meningitidis .
ET-37 complex meningococci, defined by multilocus enzyme
electrophoresis, have been isolated on different
continents . Twenty-six different Opa proteins have been
observed within strains of the ET-37 complex isolated
between the 1960s and the 1980s, although individual
strains have only four opa genes per chromosome . In
this work the opa genes of four closely related ET-37
complex N . meningitidis strains recently isolated from
Mali, West Africa were characterized and compared with
the opa genes of strain FAM18, an ET-37 complex isolate
from the USA . DNA sequence analysis and Southern blot
experiments indicated that recombinational reassortment,
including gene duplication and import by horizontal
genetic exchange, has occurred in the opa genes within
the ET-37 complex, resulting in two partially different
Opa repertoires being present in FAM18 and the Mali
isolates . Using synthetic peptides derived from the
hypervariable (HV) regions of opa genes, the epitopes
for nine mAbs were mapped . These bacteria, isolated on
different continents, contain both shared and unique opa
HV regions encoding epitopes recognized by mAbs and show
evidence of recombinational reassortment of the HV
regions.
JAMA, 1998 Feb 11, 279(6), 435 - 9
Efficacy of meningococcal vaccine and barriers to
vaccination; Rosenstein N et al.; CONTEXT: Use of the
quadrivalent meningococcal vaccine for control of
outbreaks has increased in recent years, but the
efficacy of meningococcal vaccine during mass
vaccination campaigns in US civilian populations has not
been assessed . OBJECTIVES: To evaluate the efficacy of
the quadrivalent meningococcal vaccine against serogroup
C meningococcal disease in a community outbreak setting
and to evaluate potentially modifiable barriers to
vaccination in an area with persistent meningococcal
disease following immunization . DESIGN: Matched
case-control study of vaccine efficacy using cases of
serogroup C meningococcal disease in persons eligible
for vaccination during mass vaccination campaigns .
Control patients were matched by neighborhood and age .
The control group was used to identify possible barriers
to vaccination . SETTING: Gregg County, Texas,
population 106076, from 1993 to 1995 . PARTICIPANTS: A
total of 17 case patients with serogroup C meningococcal
disease eligible for vaccine and 84 control patients .
MAIN OUTCOME MEASURES: Vaccine efficacy and risk factors
associated with nonvaccination . RESULTS: Vaccine
efficacy among 2- to 29-year-olds was 85% (95%
confidence interval, 27%-97%) and did not change in
bivariate analyses with other risk factors that were
significant in univariate analysis . Among control
patients, older age was strongly associated with
nonvaccination; vaccination rates for 2- to 4-year-olds,
5- to 18-year-olds, and 19- to 29-year-olds were 67%,
48%, and 20%, respectively (chi2 for linear trend,
P=.01) . CONCLUSIONS: The meningococcal polysaccharide
vaccine was effective against serogroup C meningococcal
disease in this community outbreak . Although specific
barriers to vaccination were not identified, older age
was a risk factor for nonvaccination in the target
population of 2- to 29-year-olds . In future outbreaks,
emphasis should be placed on achieving high vaccination
coverage, with special efforts to vaccinate young
adults.
J Infect Dis, 1998 Feb, 177(2), 497 - 500
New Zealand epidemic of meningococcal disease identified
by a strain with phenotype B:4:P1.4; Martin DR et al.;
New Zealand is experiencing an epidemic of serogroup B
meningococcal disease, which has taken the rate of
disease from an average of 1.5/100,000 population in the
preepidemic years of 1989 and 1990 to 14.0/100,000 in
1996 . Sterile-site isolates of Neisseria meningitidis
from cases of invasive disease have been phenotypically
characterized by serogrouping, serotyping, and
serosubtyping, revealing the involvement of a strain
with phenotype B:4:P1.4 . Macrorestriction analysis
using pulsed-field gel electrophoresis on 667
meningococci isolated from cases during the epidemic has
identified the clonal relationship of meningococci
expressing the PorA P1.4 antigen . Multilocus enzyme
electrophoresis has shown the epidemic strain B:4:P1.4
to belong to lineage III . The recorded characteristics
of New Zealand's epidemic are consistent with previous
serogroup B epidemics in other parts of the world.
J Antimicrob Chemother, 1997 Dec, 40(6), 895 - 7
Meropenem susceptibility of Neisseria meningitidis and
Streptococcus pneumoniae from meningitis patients in The
Netherlands; van de Beek D et al.; In-vitro
susceptibility of 299 Neisseria meningitidis and 157
Streptococcus pneumoniae strains from meningitis
patients in The Netherlands in 1993 and 1994 to
meropenem was determined using the Etest .
Susceptibility to penicillin, ceftriaxone, and
chloramphenicol was also determined . Rifampicin
susceptibility was additionally tested for N .
meningitidis . Of the meningococci, 4.3% were of
intermediate resistance to penicillin and 0.3% were
resistant to rifampicin . One pneumococcal isolate
(0.6%) was of intermediate resistance to penicillin .
All strains were susceptible to meropenem . We conclude
that meropenem is in vitro highly active against N .
meningitidis and S . pneumoniae.
Heart Lung, 1997 Nov-Dec, 26(6), 492 - 500
Case study of fulminant meningococcal septicemia
diagnosed in a twenty-year-old woman with bulimia
nervosa; Pierson DM; Fulminant meningococcal septicemia
accounts for 5% to 10% of patients with meningococcemia;
it is rapidly progressive and is associated with high
morbidity and mortality rates . The highest
meningococcal incidence is found in the 6- to
20-month-old age group; whereas immunoincompetence is
suggested in adults with the condition . Coincidentally,
eating disorders are purported to be the most prevalent
psychiatric or behavioral disturbance affecting
adolescents, and studies indicate that vulnerability to
infectious disease may be present in this group as a
result of a subclinical malnutrition state . I report a
case of fulminant meningococcal septicemia in a patient
with a comorbid eating disorder of bulimia nervosa, who
had a tumultuous disease course, and with rapid and
aggressive management of her condition--an impressive
recovery.
Zh Mikrobiol Epidemiol Immunobiol, 1995 Jul-Aug, (4), 67
- 71
{The relationship between the immunological efficacy of
a dried meningococcal group-A polysaccharide vaccine and
the molecular parameters of the group-A polysaccharide};
Alliluev AP et al.; This work deals with the problem of
relationship between the molecular parameters of group A
meningococcal polysaccharide and its immunological
effectiveness for laboratory animals and humans . The
depolymerization of group A polysaccharide contained in
the vaccine leads to a decrease in its capacity of
inducing the production of hemagglutinating (19S and 7S)
and bactericidal IgA antibodies in humans, as well as
inducing an increase in the number of cells producing
IgA antibodies in the spleen of immunized mice and the
appearance of circulating IgA antibodies in their sera .
As shown in this investigation, fully developed immune
response to group A meningococcal vaccine may be
achieved in humans only if the content of group A
high-molecular polysaccharide in the vaccine is not less
than 70% . Mice have been recommended as an experimental
model for the prognostication of the effectiveness of
meningococcal polysaccharide vaccines and for their
control in the process of manufacture instead of
currently used titration of bacteriolysins in the sera
of immunized humans.
Zh Mikrobiol Epidemiol Immunobiol, 1995 Jul-Aug, (4), 17
- 9
{The range of individual sensitivity to adhesion by
Neisseria meningitidis serogroup B in young men};
Rumiantsev SN et al.; 5,340 young adult males, including
5,149 healthy persons, 141 N . meningitidis carriers, 25
patients with generalized meningococcal infection and 6
patients with nasopharyngitis of meningococcal etiology,
were examined . The study revealed that red blood cells
of 17.4% of healthy persons were highly sensitive to
N.meningitidis adhesion (adhesion indices equal to 0.25
and less), red blood cells of 20.4% of persons had low
sensitivity to N.meningitidis adhesion (adhesion indices
equal to 2 and greater) . All other persons with high
sensitivity of their red blood cells proved to be
patients with meningococcal infection or carriers of
N.meningitidis of the same group.
Lik Sprava, 1996 May-Jun, (5-6), 136 - 41
{Oculomotor disorders in the clinical picture of
bacterial meningoencephalitis}; Iarosh O et al.; The
clinical study comprising 254 patients with bacterial
meningoencephalitis (meningococcal, pneumococcal,
staphylococcal, undefined, with n = 135, 76, 43, 120
respectively) permitted identifying a syndrome of
oculomotor disturbances . It has been shown that
assessment of changes in oculomotor disturbances enables
the extent of inflammatory process, focal lesion as well
as course and outcome of bacterial meningoencephalitis
to be determined in a timely fashion.
Rev Neurol, 1997 Sep, 25(145), 1381 - 2
{Spontaneous intracranial hemorrhages in childhood};
Veira C et al.; INTRODUCTION: Spontaneous or
non-traumatic intracranial haemorrhages seen in children
of under 15 years old are most frequently due to
cerebral vascular malformations, followed at a
considerable distance by blood disorders, vasculopathies,
tumours and the complications of radio-therapy .
OBJECTIVE: To present the cases of spontaneous and
non-traumatic cerebral haemorrhage seen at our hospital
. MATERIAL AND METHODS: We reviewed all the paediatric
cases of spontaneous cerebral haemorrhage diagnosed in
our hospital over the previous sixteen years, excluding
bleeding in the neonatal period . Computerized
tomography was done in all cases, study of the
cerebrospinal fluid, angiography and/or magnetic
resonance in some cases . RESULTS: We selected 44
patients, of who the aetiology could be determined in 30
. Of these, 20 cases were due to vascular malformations,
7 were associated with haematological disorders, 2 with
cerebral tumours and one case with meningococcal sepsis
. The commonest form of presentation was that of an
acute intracranial hypertension syndrome, also showing
focal deficits, partial crises and meningism .
CONCLUSIONS: The commonest cause of spontaneous
intracranial haemorrhage in children is due to rupture
of a vascular malformation, namely an arterio-venous
malformation . Angiography and/or magnetic resonance are
the techniques of choice for diagnosis . The various
causes of disorders of haemostasia also are important in
giving rise to intracranial bleeding.
Cent Eur J Public Health, 1997 Dec, 5(4), 214 - 8
Development of the epidemiological situation in invasive
meningococcal disease in the Czech Republic caused by
emerging Neisseria meningitidis clone ET-15/37; Krizova
P et al.; Meningococcal clone ET-15/37, which appeared
as a new one in the Czech Republic in 1993, caused an
emergency epidemiological and clinical situation in
invasive meningococcal disease, characterized by a high
fatality rate (20%) compared to the "normal" fatality
rate due to "non ET-15/37" strains . Morbidity rate
increased since the first year of the new clone
occurrence and reached the peak in 1995 . This clone has
spread all over the country and investigation of the
epidemiological markers of Neisseria meningitidis
allowed to quickly recognize the emergency situation and
subsequently to provide a targeted vaccination with A +
C polysaccharide meningococcal vaccine which prevented
the spread of the disease caused by Neisseria
meningitidis C . The most frequent phenotype of ET-15/37
clone was C:2a:P1.2(P1.5) and its percentage achieved
80% of group C Neisseria meningitidis strains tested .
This antigenic shift of Neisseria meningitidis was
associated with the age shift in invasive meningococcal
disease morbidity: teenagers started to be the most
affected age group and later age group of 1-4 olds
followed with high morbidity rates . In 1995 B variant
of ET-15/37 clone, B:2a:P1.2(P1.5), appeared, causing a
high fatality rate, too . Some data are indicative of a
possible decrease in the invasive meningococcal disease
incidence in the Czech Republic; nevertheless, the
active surveillance and detailed investigation of
meningococci have to be continued . After four years
following the vaccination and chemoprophylaxis strategy
recommended in the Guidelines, set up by the National
Reference Laboratory for Meningococcal Infections in
1993, it is possible to conclude, that there have been
practically no secondary cases of invasive meningococcal
disease in the Czech Republic.
Commun Dis Rep CDR Rev, 1997 Dec 12, 7(13), R195 - 200
A retrospective survey of clusters of meningococcal
disease in England and Wales, 1993 to 1995: estimated
risks of further cases in household and educational
settings; Hastings L et al.; Information about the
epidemiology of meningococcal disease case clusters and
the risk of further cases is sparse . Data on clusters
in household and educational settings from 1 January
1993 to 31 March 1995 was requested from consultants in
communicable disease control in England and Wales
through a retrospective postal survey . Ninety-three per
cent (122/131) responded . Of the 114 cases in 45
reported clusters, 77 (67.5%) were microbiologically
confirmed . The case fatality rate in index cases was
higher than in associated cases (18.2% vs 4.5%; p =
0.02) . Five out of 11 clusters in household settings
consisted only of index and co-primary cases . No
further cases occurred within two weeks after giving
chemoprophylaxis to household contacts . The relative
risks of further cases in the week after the index case
arose were estimated to be 1200 for contacts in the
household, 160 in secondary schools, 60 in primary
schools, 1.8 in universities/colleges, and 0 in
nurseries . Between seven and 30 days the relative risks
were lower; 150 in households, and between 0 and 13 in
all other settings . Beyond 30 days, the relative risk
in the household setting was 8 and lower than this in
all other settings . The absolute risk of further cases
in the month following the index case was calculated as
210 per 100,000 in household members, 7-10/10(5) in
pupils at the same school, and 0.6/10(5) in students at
the same university or college . The current policy in
England and Wales to recommend chemoprophylaxis for
household members may prevent half of the further cases
in this setting . Raised awareness may have contributed
to the lower case fatality rate among household contacts
who developed meningococcal disease, but the number of
co-primary cases observed should prompt urgent enquiries
about current illness in household contacts of index
cases . The relative risk of further cases in preschool
groups was low and apparently unaffected by changes in
chemoprophylactic policy . The relative risk in school
settings was raised in the month following a case, but
the absolute risk was still low . Further study to
quantify the risk in university settings is needed.
Arkh Patol, 1997 Sep-Oct, 59(5), 22 - 7
{Kidney morphology in children with meningococcal
infection}; Khodasevich LS et al.; The kidneys of 30
children aged 1 month to 5 years who died of
meningococcal infection were studied . Three variants of
the kidney damage were distinguished on the basis of
morphometric parameters . These variants corresponded to
the stages of the infectious-toxic shock . The 1st
variant observed in the reversible shock stages was
characterized by arteriolar spasm and circulation shunts
. The 2nd variant corresponded to initial manifestations
of the disseminated vascular coagulation and was
characterized by a combination of spasm and paralytic
arteriola dilatation with a predominant thrombosis of
the juxtamedullar glomeruli . The 3rd variant, the stage
of the organ alterations, was followed by development of
glomerular thrombotic microangiopathy with tubular
epithelial necrosis in the proximal tubules this being
the morphological counterpart of the hemolytico-uremic
syndrome.
Klin Padiatr, 1997 Nov-Dec, 209(6), 380 - 3
{Recombinant tissue plasminogen activator in treatment
of fulminant meningococcal infection}; Winter K et al.;
This article reports about a young boy with fulminant
meningococcal septicemia . Conventional treatment with
antibiotics, intensive care and hemostatic drugs hold up
vital functions . Because of extensive purpura fulminans
with skin necrosis recombinant tissue plasminogen
activator (rt-PA) was used . Under this therapy clinical
improvement was observed.
Mol Gen Genet, 1997 Dec, 257(1), 28 - 34
Molecular divergence of the sia locus in different
serogroups of Neisseria meningitidis expressing
polysialic acid capsules; Claus H et al.; The serogroups
B, C, W135 and Y of Neisseria meningitidis express
chemically and immunologically distinct capsular
polysaccharides containing sialic acid . In the case of
serogroup B meningococci sialic acid is synthesized by
the gene products of a locus termed sia and forms the
homopolymers of the capsule . The organization of the
genes required for sialic acid synthesis in serogroups
B, C, W135 and Y was elucidated by PCR technology .
Cloning, sequencing and the functional expression of the
polysialyltransferase (PST) genes of serogroups B and C
demonstrated that the difference in capsule composition
derives from the presence of related, but distinct siaD
genes coding for PSTs . Analysis of meningococci of
serogroups W135 and Y expressing sialic acid
heteropolymers revealed that the DNA sequences of the
corresponding genetic loci in these serogroups were
highly homologous, but differed completely from the siaD
genes of serogroups B and C . This finding suggests that
enzymes unrelated to those of serogroups B and C are
required for the formation of sialic acid heteropolymers
characteristic of the capsules of serogroups W135 and Y.
Curr Opin Hematol, 1995 Sep, 2(5), 402 - 6
Disseminated intravascular coagulation; Kitchens CS;
Disseminated intravascular coagulation is the result of
a severe underlying disorder that initiates massive
activation of the coagulation system . It is always a
symptom of the underlying disorder . These disorders may
be as varied as meningococcemia and abdominal aortic
aneurysm . Disseminated intravascular coagulation is a
clinical diagnosis . Once the clinical impression has
been considered, a small number of readily available
tests will substantiate the diagnosis . Further testing
is probably not necessary and certainly not
cost-effective . Therapy for disseminated intravascular
coagulation requires 1) the correction of the underlying
problem, either by drainage of an abscess for sepsis,
evacuation of the uterus in an obstetric catastrophe, or
treatment of septicemia with antibiotics; and 2) the
concomitant restoration of the circulatory system,
perfusion, blood pressure, and electrolyte balance .
Other forms of therapy are available but are quite
secondary to these two . Success depends on the ability
to recognize and correct the cause.
J Intern Med, 1997 Dec, 242(6), 519 - 20
The usefulness of skin culture in the diagnosis of
chronic meningococcaemia; Texereau M et al.; We deal
with the second reported case of chronic
meningococcaemia in which the culture of skin biopsy led
to the diagnosis . A 46-year-old man presented a history
of recurrent fever and rash . Laboratory studies
revealed an inflammatory syndrome . Serologic tests as
well as blood culture tests were negative . The
histological examination of skin lesions revealed a
perivascular infiltrate in the dermis without any
picture of leukocytoclastic vasculitis . A culture of
skin specimen tested positive for Neisseria meningitidis
(N . meningitidis) . After a week of antibiotic
treatment, the patient recovered with no recurrence of
either fever or rash over a two year period.
J Intern Med, 1997 Dec, 242(6), 455 - 64
Hypocomplementaemia caused by C3 nephritic factors (C3
NeF): clinical findings and the coincidence of C3 NeF
type II with anti-C1q autoantibodies; Skattum L et al.;
OBJECTIVES: The main purposes were to document
manifestations associated with prolonged or clinically
unexplained C3 deficiency and to approximate how often
hypocomplementaemia of this kind is caused by C3
nephritic factors (C3 NeF), i.e . autoantibodies to
alternative pathway C3 convertases . We also wished to
distinguish between C3 NeF types I and II and to assess
coincident autoantibody responses to the collagen-like
region of C1q (C1qCLR) . SETTING: The investigation was
based on serum samples referred to a specialized
laboratory for complement analysis in the course of
several years . SUBJECTS: Twenty-five persons with C3
concentrations lower than 0.43 g L-1, a third of the
normal, were included in the study . RESULTS: Analysis
using three methods provided evidence of C3 NeF in 20
persons with equal frequencies of C3 NeF types I and II
. We also gave evidence of antibody specificity
differences for the two types of C3 NeF . Six patients
with C3 NeF type II showed antibodies to C1qCLR .
Membranoproliferative glomerulonephritis was the
predominant diagnosis and two patients had partial
lipodystrophy reflecting the well-known association
between these diseases and C3 NeF . Anaphylactoid
purpura, systemic lupus erythematosus, and severe
infection, mainly meningococcal disease, were also
observed . CONCLUSIONS: The study group was probably
fairly representative of C3 deficiency syndromes as
encountered in clinical practice . The findings
emphasize the heterogeneity of C3 NeF, and that acquired
C3 deficiency syndromes caused by C3 NeF should perhaps
be considered more often in diagnostic work.
Presse Med, 1997 Oct 25, 26(32), 1516 - 9
{Rapid epidemiological characterization of Neisseria
meningitidis using polymerization chain reaction from
biological samplings}; Giorgini D et al.; OBJECTIVES:
Due to the spread of the meningococcal infections, a
good epidemiological surveillance is needed .
Prophylactic measures should be undertaken because of
the high transmissibility of these bacteria . One
problem which hinders the epidemiological
characterization is that the responsible strain should
be isolated . The aim of this work is to develop a rapid
and non culture typing method of Neisseria meningitidis
. METHODS: Six cerebrospinal fluids were obtained from 5
different patients with meningococcal meningitis . A
specific locus, pil A, for N . meningitidis was
amplified by polymerization chain reaction (PCR) . The
polymorphism of this locus was then analyzed by
digesting the PCR products with one of three different
restriction enzymes . RESULTS: The polymorphism of this
locus allowed us to establish the clonal relationships
between the meningococcal strains involved in the
infection . Three CSF corresponded to epidemiological
strains . CONCLUSION: This typing method allows a rapid
and less expensive epidemiological characterization of
meningococcal infections . Moreover, it is a non culture
typing method.
Scand J Infect Dis, 1997, 29(5), 479 - 83
Purpura fulminans in pneumococcal sepsis: case report
and review; Carpenter CT et al.; Purpura fulminans is
classically defined by ecchymotic skin lesions, fever,
and hypotension . The majority of cases occur in
association with bacterial sepsis, and disseminated
intravascular coagulation (DIC) is usually present .
Prompted by our experience with a patient with
pneumococcal sepsis and purpura fulminans in whom
hypotension was never observed, we evaluated the
important parameters of sepsis in reports of this
syndrome . 42 additional cases of pneumococcal
bacteremia and purpura fulminans were identified .
Hypotension was present in only 51% . Although DIC was
present in 85% of patients, hypofibrinogenemia was
documented in only 26% . By contrast, both hypotension
and hypofibrinogenemia are present in the vast majority
of patients described with purpura fulminans in
association with meningococcal sepsis . These data
confirm that hypotension is not a necessary feature of
the syndrome of purpura fulminans associated with
pneumococcal sepsis and suggest further that qualitative
or quantitative differences exist in the DIC cascade of
pneumococcal vs meningococcal sepsis.
J Laryngol Otol, 1997 Oct, 111(10), 913 - 6
Acute otitis media and otitis media with effusion in
children with bacterial meningitis; Richardson MP et
al.; Acute otitis media and otitis media with effusion (OME)
have often been observed in children with bacterial
meningitis . OME has also been proposed as the mechanism
of reversible hearing loss after meningitis . In this
controlled study, children with acute bacterial
meningitis were studied using auditory brainstem
responses (ABR), otoacoustic emissions, tympanometry and
otoscopy . An age- and sex-matched control was recruited
for each patient and the incidence of acute otitis media
and OME was compared between the two groups . One
hundred and twenty-four children with meningitis were
studied . Ninety-two children (74 per cent) had
meningococcal meningitis . Five patients (4 per cent)
had conductive hearing loss (ABR threshold > or = 30 dB
HL) at the time of discharge from hospital . None of the
patients or controls had acute otitis media . Patients
and controls were well matched for risk factors for OME
and the prevalence of middle ear effusion in patients
and controls was 7.2 per cent and 11.3 per cent
respectively . The relative risk of OME in the children
with meningitis was 0.64 (95 per cent confidence
interval 0.29 to 1.42) . After nine months, three of the
five children with meningitis and conductive hearing
loss had regained normal hearing . In contrast to
previous reports, there was no relationship between
bacterial meningitis and acute otitis media or OME in
this study . Nevertheless, coincidental conductive
hearing defects were identified as the cause of
reversible hearing loss in three patients.
Enferm Infecc Microbiol Clin, 1997 Oct, 15(8), 414 - 7
{A clone of Neisseria meningitidis serogroup C was
responsible in 1994 of an unusual high rate of strains
with a moderate resistance to penicillin in Caracas
(Venezuela)}; Toro S et al.; BACKGROUND: The aim of the
study was to analyse meningococcal strains isolated from
patients in Caracas (Venezuela) with epidemiological
markers and to determine their susceptibility to
antimicrobial agents . METHODS: We analyzed 29
meningococcal clinical strains isolated during 1994 in
Caracas by serogrouping, serotyping and subserotyping,
multilocus enzyme analysis (MEE), ribotyping and pulse
field electrophoresis (PFGE) profile . We also
determined the Minimal Inhibitory Concentration (MIC) to
5 antimicrobial agents . RESULTS: Twenty four (82.7%)
were group C meningococcal strains . All group C
meningococci were characterized as C: 2b: P1.5,
belonging to the same electrophoretic type (ET) by MEE
and showing the same profile by PFGE by using Bg/II
endonuclease restriction enzyme . These group C
meningococci showed two different patterns by ribotyping,
with only one band difference . All Group C and one
group B N . meningitidis isolates were moderately
resistant to penicillin (MIC > or = 0.12 mg/l) .
CONCLUSIONS: During 1994 an unusual high incidence of
meningococcal strains moderately resistant to penicillin
(PenMR) was detected in Caracas (Venezuela) . A clone of
C: 2b: P1.5 meningococci seem to be responsable for this
high incidence of PenMR isolates.
Infect Immun, 1998 Jan, 66(1), 213 - 7
Periplasmic superoxide dismutase in meningococcal
pathogenicity; Wilks KE et al.; Meningococcal sodC
encodes periplasmic copper- and zinc-cofactored
superoxide dismutase (Cu,Zn SOD) which catalyzes the
conversion of the superoxide radical anion to hydrogen
peroxide, preventing a sequence of reactions leading to
production of toxic hydroxyl free radicals . From its
periplasmic location, Cu,Zn SOD was inferred to acquire
its substrate from outside the bacterial cell and was
speculated to play a role in preserving meningococci
from the action of microbicidal oxygen free radicals
produced in the context of host defense . A sodC mutant
was constructed by allelic exchange and was used to
investigate the role of Cu,Zn SOD in pathogenicity .
Wild-type and mutant meningococci grew at comparable
rates and survived equally long in aerobic liquid
culture . The mutant showed no increased sensitivity to
paraquat, which generates superoxide within the cytosol,
but was approximately 1,000-fold more sensitive to the
toxicity of superoxide generated in solution by the
xanthine/xanthine oxidase system . These data support a
role for meningococcal Cu,Zn SOD in protection against
exogenous superoxide . In experiments to translate this
into a role in pathogenicity, wild-type and mutant
organisms were used in an intraperitoneal mouse
infection model . The sodC mutant was significantly less
virulent . We conclude that periplasmic Cu,Zn SOD
contributes to the virulence of Neisseria meningitidis,
most likely by reducing the effectiveness of toxic
oxygen host defenses.
Ren Fail, 1997 Nov, 19(6), 807 - 10
Outcome of acute renal failure in meningococcemia;
Marotto MS et al.; We studied 28 consecutive patients
(18 males and 10 females), 1-32 years of age, admitted
to the intensive care unit from January 1989 to July
1995, with acute renal failure (ARF) due to
meningococcal septicemia . All patients were treated
with dexamethasone, penicillin, and/or chloramphenicol .
Twenty-two patients presented septic shock and needed
fluid replacement and vasoactive drugs . Acute renal
failure was oliguric in 67.8% . Maximum levels of blood
urea and serum creatinine were 210.3 +/- 26.6 mg/dL and
6.9 +/- 1.3 mg/dL, respectively . Metabolic acidosis was
observed in 89.3% and hyperkalemia in 43% . The
fractional excretion of sodium on day 1 was high (9.9
+/- 0.6%) . The urinalysis did not show trace protein,
but hematuria was positive in 81% . The mortality rate
was 63.3% . In the 10 survivors, oliguria was present
for a period of 12.7 +/- 2.4 days, and the period to
reach a normal serum creatinine level was 20.2 +/- 4.7
days, although in two female patients, 7 and 17 years
old, the elevated serum creatinine persisted . Renal
biopsy was performed in one of these patients which
revealed bilateral cortical necrosis . These data show
that acute renal failure in meningococcemia presents
high mortality rate associated to shock; 80% of the
survivors recover renal function; and bilateral cortical
necrosis occurred in one patient in this series.
Enferm Infecc Microbiol Clin, 1997 Aug-Sep, 15(7), 369 -
72
{Meningococcal infection caused by Neisseria
meningitidis serogroup C}; Ursua MI et al.; BACKGROUND:
In recent years an increase has been observed in the
prevalence of meningococcal infection by Neisseria
meningitidis serogroup C and in the appearance of
strains with moderate resistance to penicillin .
PATIENTS AND METHODS: A microbiologic study of the cases
of meningococcal infection of serogroup C treated from
1995 to 1996 in the health care area of Ferrol (La
Coruna, Spain) was carried out . RESULTS AND
CONCLUSIONS: Twenty-nine cases were detected in 1995 and
28 in 1996 . Meningococcal infection was observed in
patients ranging from 8 months to 21 years of age (mean
5.7 years) . Distribution by sex was homogeneous . Two
patients died . According to the clinical presentation,
11 were sepsis (38%), 4 meningitis (14%) and 14 both
processes (48%) . In 4 LCR samples, the analytical study
was normal with posterior positive culture results . The
detection of bacterial antigen by latex agglutination in
CSF only detected 32% of the cases . MIC study
determined that 11 strains (38%) presented moderate
resistance to penicillin, 9 with a MIC of 0.12
microgram/ml, one with a MIC of 0.25 microgram/ml and
another with a MIC of 0.5 microgram/ml . In all the
cases the strains were sensitive to cefotaxime (MIC < or
= 0.06 microgram/ml) and rifampicin (MIC < or = 0.5
microgram/ml) . All the strains belonged to serogroup C
serotype 2b, serosubtype P1.2,5 . During the study
period 4 additional cases of meningococcal disease by
serogroup B were observed.
Acad Emerg Med, 1997 Dec, 4(12), 1129 - 36
Adverse outcomes of managed care gatekeeping; Young GP
et al.; OBJECTIVES: To determine whether telephone
preauthorization for reimbursement of ED care (medical
"gate-keeping") by managed care organizations (MCOs) is
associated with adverse outcomes . METHODS: A structured
review was performed of case reports solicited during
1994 and 1995 with possible adverse outcomes related to
managed care gatekeeping . Gatekeeping was defined as
the requirement imposed by an MCO that ED staff contact
on-call gatekeepers (i.e., clinical or nonclinical MCO
personnel) to request preauthorization for ED treatment
(a requirement that such MCOs enforce by refusing
payment for the ED care unless preauthorization is
obtained) . Cases in which gatekeeper denial of
preauthorization occurred were sought . Two physicians
agreed on patient eligibility and classification
criteria, then independently, retrospectively classified
case reports identified as MCO ED payment denials into 1
of 4 categories: 1) adverse outcome; 2) patient placed
at increased risk of death or disability; 3) "near miss"
(emergency physicians prevented adverse outcome by
caring for patient despite denial); and 4) none of the
above . RESULTS: Of the 143 cases reviewed, 29 reports
represented MCO ED payment denial . Of these 29 eligible
cases, there were 4 (14%) patients with adverse
outcomes, 4 (14%) patients placed at increased risk, and
21 (72%) near misses . All of the 29 cases came from
different EDs, representing 9 different states, with the
majority from California . Adverse outcomes included
respiratory failure from fulminant meningococcemia,
hypovolemic syncope from ruptured ectopic pregnancy,
hypovolemic arrest from vascular fibroid hemorrhage
necessitating emergency hysterectomy, and prolonged
postoperative course following ruptured duodenal ulcer .
Patients placed at increased risk were diagnosed as
having epiglottitis, myocardial infarction, ruptured
ectopic pregnancy, and delayed treatment of hip septic
arthritis . Near misses included diagnoses of ectopic
pregnancy (n = 2), pneumothorax (n = 2), alcohol
withdrawal seizures and pancreatitis necessitating
intensive care unit admission, appendicitis, bacterial
meningitis, cerebrovascular accident, cryptococal
meningitis in immuno comprised host, endocarditis,
incarerated inguinal hernia, meningocococemia,
meninoccocal meningitis, peritonsillar abscess,
pneumococcal meningitis, ruptured abdominal aortic
aneurysm, shock from gastrointestinal bleeding, small
bowel obstruction, schizophrenic crisis resulting in
psychiatric hospitalization, suicidal depression
resulting in psychiatric hospitalization, and unstable
angina . CONCLUSION: Adverse outcomes occur with MCO
gatekeeping, Although the present study cannot ascertain
whether this is a frequent event or a rare one, the
safety of MCO gatekeeping deserves further study.
Thorax, 1997 Oct, 52(10), 927 - 9; discussion 926-7
Three cases of meningococcal pneumonia; Jones EM et al.;
Three cases of pneumonia due to Neisseria meningitidis
are described . In all three cases the organism was
isolated only from blood cultures, but in the presence
of good clinical and radiological evidence of pneumonia
. The isolates belonged to three different serogroups: B
type 2b, C, and Y . The cases illustrate the fact that N
meningitidis can cause pneumonia and that culture of
blood plays an important part in the diagnosis .
Clinically there is nothing to differentiate
meningococcal pneumonia from other causes of community
acquired pneumonia . Predisposing factors include
aspiration, immunosuppression, influenza, and adenovirus
infections . When diagnosed, pneumonia due to N
meningitidis should be notified and prophylaxis given as
for meningitis or septicaemia.
Med Microbiol Immunol (Berl), 1997 Oct, 186(2-3), 159 -
66
Functional characterization of an isogenic meningococcal
alpha-2,3-sialyltransferase mutant: the role of
lipooligosaccharide sialylation for serum resistance in
serogroup B meningococci; Vogel U et al.; The neisserial
alpha-2,3-sialyltransferase, which is encoded by the lst
gene, terminally links sialic acid to the lacto-N-neotetraose
residue of neisserial lipooligosaccharide (LOS) . We
used the recently published nucleotide sequence of the
neisserial lst gene to construct an isogenic serogroup B
meningococcal lst mutant by insertion of a kanamycin
resistance gene . The resulting lst mutant expressed the
unsialylated lacto-N-neotetraose structure . Using
bactericidal assays and an infant rat model of
meningococcal infection, we were able to demonstrate
that lst mutation, in contrast to galE mutation, which
results in a truncated LOS, or to siaD mutation, which
results in loss of the capsule, neither had an effect on
resistance to normal human serum, nor did it impair the
ability of meningococci to spread systemically in the
non-immune host . The lst mutant was serum resistant
despite of the fact that the central factor of
complement activation, C3b, was deposited on the lst
mutant as efficiently as it was on the galE mutant .
Thus, the terminal sialic acid residue linked to the
wild-type LOS inhibited C3b deposition on the
meningocuccus . However, in contrast to the galE mutant,
where C3b deposition is promoted by IgM binding, the lst
mutant's surface is not a target for IgM molecules .
Thus, the lacto-N-neotetraose residue of neisserial LOS
alone, without the presence of terminal sialic acid, is
sufficient to block IgM epitopes either on the LOS
itself, or on other surface molecules . Our data provide
further insight into the complex interplay of capsular
and LOS sialic acids in serogroup B meningococci with
host effector mechanisms, and suggest that LOS
sialylation in meningococci is of a less central
importance as it is in gonococci.
Acta Paediatr, 1997 Nov, 86(11), 1263 - 6
Severe skin loss after meningococcal septicaemia:
complications in treatment; Huang S et al.;
Meningococcal septicaemia can lead to purpura fulminans
with subsequent full thickness skin loss and deep muscle
damage . The case reports on two infants who recovered
from such a severe episode are used to describe post-septicaemic
procedures and complications encountered in nursing
care, psychological support and rehabilitation, with the
main focus on surgery . Skin grafting is complicated by
contaminated and contracting wound areas . Extensive
tissue necrosis required leg amputations . Cultured
keratinocytes in one of the patients were found to be
too vulnerable . It has still to be proven whether more
radical early-stage fasciotomies can limit skin and
muscle necrosis . Patients with meningococcal
septicaemia are subject to a high number of
complications that are optimally treated in a burns unit
. These patients require up-to-date knowledge of
constantly evolving treatment possibilities and a
high-level collaboration of all medical fields involved.
J Clin Microbiol, 1997 Dec, 35(12), 3215 - 9
Confirmation of suspicious cases of meningococcal
meningitis by PCR and enzyme-linked immunosorbent assay;
Saunders NB et al.; A significant problem in efficacy
trials of meningococcal vaccines has been accurate
identification of all cases of meningococcal disease
that occur in study populations . The accuracy of case
determination would be improved by utilizing methods
which confirm or disprove suspicious cases of
meningococcal disease that are culture negative . A
collection of serum and cerebrospinal fluid (CSF)
samples from a meningococcal vaccine field trial
performed in Iquique, Chile, were utilized to assess the
status of patients for whom cultures, Gram stains, and
clinical evaluations for meningococcal disease were
available . Nested PCRs (nPCRs) for amplification of
Neisseria meningitidis DNA in CSF samples and
enzyme-linked immunosorbent assays (ELISAs) for
quantification of serum immunoglobulin G antibodies
specific for N . meningitidis were used in combination
to confirm or eliminate cases classified by physicians
as suspicious for meningococcal disease . Samples from
12 of 79 patients suspected of having meningococcal
meningitis tested positive by both methods; specimens
from 61 of the 79 were negative by both methods; and
samples from 6 patients yielded ambiguous results, and
these cases remained unconfirmed . Direct sequence
analysis of amplified DNA from patients suspected of
having meningococcal disease confirmed that 2 of the 12
newly confirmed cases were not attributable to the
typical epidemic strain (B:15:P1.{7},3) while the others
were due to the epidemic strain . A combination of nPCR
and ELISA reduced the number of suspicious cases in this
study from 79 to 6, thereby improving the potential for
assessment of vaccine efficacy . Molecular
identification by nPCR in conjunction with immunological
assessment of patient response could be considered
diagnostic of disease in future testing of meningococcal
vaccines to improve efficacy analyses.
FEBS Lett, 1997 Nov 10, 417(2), 253 - 9
Identification of potential ferric binding residues in
the iron-binding protein of pathogenic Neisseria
meningitidis through structure-based multiple sequence
alignments; Gorinsky B et al.; The ferric iron-binding
proteins of pathogenic Neisseria display structural and
metal-binding properties characteristic of the
transferrin family . In the absence of structural data
for the ferric iron-binding proteins, spacial folding
templates have been derived for the meningococcal
protein from complete and partial structure-based
multiple sequence alignments with structurally related
proteins . The templates have been used to identify a
number of potential iron-binding residues . These
include four residues that are identical with the iron
coordinating ligands of transferrin, but only two reside
within equivalent structural elements.
FEMS Immunol Med Microbiol, 1997 Oct, 19(2), 159 - 67
Analysis of the human Ig isotype response to individual
transferrin binding proteins A and B from Neisseria
meningitidis; Johnson AS et al.; Subcapsular antigens,
including transferrin binding proteins, are being
considered as potential vaccines against serogroup B
meningococci . This study examined the human isotype
antibody responses in cases of meningococcal disease to
meningococcal TbpA (transferrin binding protein A) and
TbpB (transferrin binding protein B) from two strains (SD
and B16B6) expressing high and low molecular mass TbpB
respectively . TbpA isolated from both strains were
recognised more frequently and higher durable ELISA
absorbance values were detected than those detected
against TbpB from either strain . These antibody
responses to Tbps were independent of the infecting
meningococcal strain type . The antibody response to the
four proteins was highly variable between individuals
and differed significantly against all four antigens .
The variability of immune responses to each Tbp from the
two strains suggests that a successful vaccine would
need to include TbpA and TbpB from a number of strains.
Infect Immun, 1997 Dec, 65(12), 5184 - 90
Human B- and T-cell responses after immunization with a
hexavalent PorA meningococcal outer membrane vesicle
vaccine; van der Voort ER et al.; The PorA protein from
Neisseria meningitidis, a potential vaccine candidate,
induces human bactericidal antibodies which are
serosubtype specific . We developed a hexavalent PorA
outer membrane vesicle vaccine based on reference strain
H44/76 . This vaccine contains the six most prevalent
PorA serosubtypes as found in many countries . We
previously reported on the immune responses of 20 adult
volunteers after a single immunization with this vaccine
. In this study, the B- and T-cell responses in three
adult volunteers were studied after three consecutive
immunizations (0, 2, and 11 months) . The first
immunization induced a strong B-cell response resulting
in high immunoglobulin G levels in an outer membrane
vesicle enzyme-linked immunosorbent assay . At least a
fourfold increase in bactericidal activity was observed
against the majority (four to six) of the vaccine
antigens compared to prevaccination titers .
Immunodominance was observed for one or two of the PorAs
in the bactericidal assay with a set of six isogenic
H44/76-derived PorA target strains . These strains carry
the individual PorAs as present in the vaccine . The
second and third immunizations did not induce a further
increase in the immune responses . A decline in time
with respect to PorA-specific antibodies was observed
after each immunization . These observations were
reflected by the T-cell proliferation responses . Two
additional sets of isogenic H44/76-derived mutant
strains were used to study the specificity and/or
cross-reactivity of the induced bactericidal antibodies
. These target strains differ only in expressing mutant
family variants of either PorA P1.7,16 or P1.5,10, both
present in the PorA vesicle vaccine . The bactericidal
antibody responses found were directed predominantly
against the P1.7 (loop 1 of P1.7,16) and the P1.10 (loop
4 of P1.5,10) epitopes . This indicates that different
portions of PorA were involved in the induction of
bactericidal antibodies depending upon the PorA
serosubtype.
Lancet, 1997 Nov 29, 350(9091), 1590 - 3
Use of protein-C concentrate, heparin, and
haemodiafiltration in meningococcus-induced purpura
fulminans; Smith OP et al.; BACKGROUND: Inflammatory and
coagulation processes are both affected in
meningococcaemia . Severe acquired protein-C deficiency
in meningococcaemia is usually associated with
substantial mortality: in survivors, skin grafts,
amputation, and end-organ failure are not uncommon .
Protein C is a natural anticoagulant and also has
important anti-inflammatory activity . We assessed the
effects of early replacement therapy with protein-C
concentrate together with continuous veno-venous
haemodiafiltration and conventional treatment in
meningococcaemia . METHODS: 12 patients aged between 3
months and 27 years with meningococcaemia and severe
acquired protein-C deficiency (mean 0.20 IU/mL) were
studied . All patients had septic shock, widespread
purpura, skin necrosis, and disseminated intravascular
coagulopathy . After a test dose of protein-C
concentrate, patients received a continuous infusion
with the dose adjusted daily to keep the plasma
concentration between 0.8 and 1.2 IU/mL . 11 patients
were given unfractionated intravenous heparin (10-15 IU
kg-1 h-1) . Nine patients had haemodiafiltration and one
had peritoneal dialysis . The Glasgow meningococcal
septicaemia prognostic score and the paediatric risk of
mortality score predicted a minimum mortality of 80% and
57%, respectively . FINDINGS: No patient died . No
adverse reactions to the treatment were seen . Two
patients had lower-limb amputations, one of whom had a
thrombotic cerebrovascular accident; both patients had
received the protein-C concentrate and heparin later
than the rest of the group (60 h {16.97} vs 12 h {3.13})
. One patient developed chronic renal failure despite
receiving protein-C infusion 15 h after admission .
INTERPRETATION: The acquired severe deficiency of
protein C in meningococcaemia contributes to the
pathogenesis of the thrombotic necrotic lesions in the
skin and other organs and probably has an important role
in the inflammatory response . Protein-C therapy is
merely one approach to improve the host response in this
syndrome . We suggest that a double-blind, randomised,
controlled multicentre trial is needed to confirm our
results.
Lancet, 1997 Nov 15, 350(9089), 1439 - 43
Preliminary evaluation of recombinant amino-terminal
fragment of human bactericidal/permeability-increasing
protein in children with severe meningococcal sepsis;
Giroir BP et al.; BACKGROUND: Meningococcal sepsis
remains an important cause of morbidity and mortality .
We hypothesised that children with severe
meningococcaemia might benefit from inhibition of the
inflammatory processes thought responsible for fulminant
disease . rBPI21 is a recombinant, N-terminal fragment
of human bactericidal/permeability-increasing protein,
which kills meningococci and binds to and clears
bacterial endotoxin, these being the primary inducers of
the systemic inflammation . The aim of this study was to
determine the safety and kinetics of rBPI21 in children
with severe meningococcaemia and to make a preliminary
assessment of clinical outcome . METHODS: In this
open-label, dose-escalation, phase I/II trial in severe
meningococcaemia (Glasgow meningococcal prognostic
septicaemia score {GMSPS} > or = 8), 26 patients aged
1-18 years, who had received their first dose of
antibiotics no more than 8 hours earlier were given
rBPI21 by infusion at total doses of 1.0, 2.0, and 4.0
mg/kg . FINDINGS: The patients had significantly raised
plasma concentrations of bacterial endotoxin and
cytokines . Peak and steady state BPI concentrations
were comparable with pharmacokinetic data in healthy
adults . All complications were compatible with the
expected pattern for severe meningococcal sepsis . Only
one patient died . This outcome was found to compare
favourably with a predicted mortality of > or = 30% by
GMSPS, > or = 15% by plasma endotoxin values, > or = 28%
by plasma interleukin-6 concentrations, 29-49% by
severity of coagulopathy, and 20% (11/54) by comparison
with recent historical patients consecutively treated in
participating centres before this study .
INTERPRETATION: This, the first clinical trial or
rBPI21, shows that rBPI21 can be safely administered to
children with severe meningococcaemia and that the
pharmacokinetics are consistent with patterns seen in
healthy adults . Predicted mortality, on the basis of
GMSPS, laboratory indices of inflammation and
coagulopathy, and historical controls, was for between
four and eight deaths . These findings have prompted a
phase III randomised trial.
J Infect Dis, 1997 Nov, 176(5), 1285 - 92
Interaction of Neisseria maningitidis with the
components of the blood-brain barrier correlates with an
increased expression of PilC; Pron B et al.; A fatal
untreated case of fulminant meningococcemia was examined
to investigate the crossing of the blood-brain barrier
(BBB) by Neisseria meningitidis . Microscopic
examination showed bacteria in vivo adhering to the
endothelium of both the choroid plexus and the meninges
. Comparison of the isolates cultivated from the blood
and the cerebrospinal fluid (CSF) revealed no antigenic
variation of the pilin or the class 5 protein, whereas
the expression of the PilC protein was greater in the
CSF and the choroid plexus than in the blood . This was
due to an increased activity of one of the pilC
promotors . This higher expression of PilC correlated in
vitro with greater adhesiveness to endothelial cells . A
mutation in the single pilC locus of this strain
abolished in vitro pilus-mediated adhesion to
endothelial cells . These data suggest that PilC plays
an important role in the crossing of the BBB, likely
through pilus-mediated adhesion.
J Infect Dis, 1997 Nov, 176(5), 1277 - 84
Molecular epidemiology of sporadic (endemic) serogroup C
meningococcal disease; Raymond NJ et al.; Understanding
the basis of sporadic (endemic) meningococcal disease
may be critical to prevention of meningococcal epidemic
outbreaks and to understanding fluctuations in incidence
. Active, prospective, population-based surveillance and
molecular epidemiologic techniques were used to study
sporadic serogroup C meningococcal disease in a
population of 2.34 million persons (Atlanta area) .
During 1988-1994, in which no outbreaks or case clusters
were reported, 71 patients developed sporadic serogroup
C meningococcal disease (annual incidence, 0.51/100,000)
. Eighty-three percent of patients were >2 years old .
By multilocus enzyme electrophoresis, pulsed-field gel
electrophoresis, and serotyping, 84% (52/62) of the
isolates available for study were identical or closely
related members of the electrophoretic type 37 (ET 37)
complex responsible for multiple serogroup C outbreaks
in the United States in the 1990s . Sporadic disease
caused by 9 clonal strains occurred over periods up to 4
years and accounted for 45% (28/62) of cases . Sporadic
serogroup C meningococcal disease was most often due to
a limited number of related strains that appear to
slowly circulate in the population.
Mil Med, 1997 Nov, 162(11), 769 - 72
Primary meningococcal arthritis: case report and review
of the literature; Wells M et al.; Meningococcal
arthritis is a recognized manifestation of Neisseria
meningitidis infection, the presentation of which may be
confusing . Although arthritis occurs in the setting of
meningococcal meningitis, it may also be seen as a
primary event without neurological involvement and with
or without cutaneous manifestations . We describe a
patient with primary meningococcal arthritis and review
the literature relating to the clinical types and
pathogenic mechanisms . Comparisons of patient series
from 1980 to the present with those reported before 1980
are described.
Microbiologia, 1997 Sep, 13(3), 337 - 42
Moderate resistance to penicillin in Neisseria
meningitidis; Saez Nieto JA et al.; Meningococcal
moderate resistance to penicillin (MICs 0.12 to 1 mg/l)
was rarely reported before the 1980's in Spain . The
frequency of isolation of resistant strains increased
from 0.4% in 1985 to 42.6% in 1990 . In the last few
years, these strains have been reported in several
countries, which suggests a change in the meningococcal
response to penicillin . The resistance is due, at least
in part, to a decreased affinity of penicillin binding
protein 2 (PBP2) for penicillin . This decreased
affinity has also been found in commensal Neisseriae .
Population genetic studies demonstrate that
recombinational events, replacing parts of the PBP2 gene
by the corresponding regions of commensal species,
followed by a rapid spread of the clones could be the
origin of such resistant strains.
Infect Immun, 1997 Nov, 65(11), 4836 - 42
Interaction of Neisseria meningitidis with a polarized
monolayer of epithelial cells; Pujol C et al.; An
important step in the pathogenesis of Neisseria
meningitidis is the crossing of two cellular barriers,
one in the nasopharynx and one in the brain . To
approach the mechanisms by which this bacterium can
achieve these goals, we studied the interactions between
N . meningitidis and a monolayer of polarized tight
junction-forming T84 cells grown on filter units . A
capsulated, piliated, Opa-, and Opc- N . meningitidis
strain is shown to be capable of adhering to and
crossing this monolayer several orders of magnitude more
efficiently than an isogenic nonpiliated derivative .
This bacterial interaction does not affect the barrier
function of tight junctions, as assessed by (i) the
absence of modification of the transepithelial
resistance, (ii) the lack of increase of {3H}inulin
penetration across the monolayer, and (iii) the absence
of delocalization of ZO-1, a tight junction protein .
Electron microscopy studies and confocal examinations
demonstrated that N . meningitidis (i) induces
cytoskeletal rearrangements with actin polymerization
beneath adherent bacteria, (ii) is intimately attached
to the apical membrane of the cells, and (iii) can be
internalized inside cells . Immunofluorescent staining
with antipilus antibodies showed evidence that
meningococcal piliation was dramatically reduced at
later time points of bacterial cell interaction compared
to the early phase of this interaction . In addition,
adhesive bacteria recovered from an infected monolayer
are piliated, capsulated, Opa-, and Opc-, a phenotype
similar to that of the parental strain . Taken together,
these data demonstrate that following pilus-mediated
adhesion, N . meningitidis is involved in an intimate
attachment which requires a bacterial component
different from Opa and Opc and that meningococci cross a
monolayer of tight-junction-forming epithelial cells by
using a transcellular pathway rather than a paracellular
route.
Infect Immun, 1997 Nov, 65(11), 4436 - 44
Sialylation of Neisseria meningitidis
lipooligosaccharide inhibits serum bactericidal activity
by masking lacto-N-neotetraose; Estabrook MM et al.;
Exogenous sialylation of gonococcal lipooligosaccharide
causes resistance to serum bactericidal activity . The
aim of this study was to determine how
lipooligosaccharide sialylation affects the serum
sensitivities of group C Neisseria meningitidis strains
. The relationship between the degree of sialylation or
expression of the lipooligosaccharide sialic acid
acceptor, lacto-N-neotetraose (LNnT), of nine
meningococcal strains and their sensitivities to a pool
of normal human sera was assessed . All strains
expressed LNnT that was variously endogenously
sialylated . Susceptibility to serum bactericidal
activity ranged from extremely sensitive to resistant in
50% serum . For endogenously sialylated strains, the
amount of killing correlated with the amount of free
LNnT above a threshold of expression; strains that
expressed less than the threshold survived in 25% serum
. All strains added more sialic acid when they were
grown in medium that contained cytidine
monophospho-N-acetylneuraminic acid . Exogenous
sialylation reduced the expression of free LNnT and
significantly increased serum resistance . Exogenous
sialylation affected killing through both classical and
alternative complement pathways . The killing of
exogenously sialylated strains also correlated with the
amount of free LNnT . The amounts of endogenous,
exogenous, and total sialic acid bound to LNnT did not
correlate with the resistance of strains to serum
bactericidal activity; rather, the loss of free LNnT
expression by sialylation was associated with resistance
. In conclusion, the expression of free LNnT by group C
meningococcal strains is directly associated with the
amount of killing of organisms in pooled human sera .
Both endogenous and exogenous lipooligosaccharide
sialylation are associated with increased serum
resistance by masking LNnT.
Mol Microbiol, 1997 Sep, 25(6), 1047 - 64
Clonal descent and microevolution of Neisseria
meningitidis during 30 years of epidemic spread; Morelli
G et al.; Serogroup A meningococci of subgroups III,
IV-1 and IV-2 are probably descended from a common
ancestor that existed in the nineteenth century . The
10.5kb sequences spanning five distinct chromosomal
loci, encoding cell-surface antigens, a secreted
protease or housekeeping genes and intergenic regions,
were almost identical in strains of those subgroups
isolated in 1966, 1966 and 1917 respectively . During
the subsequent two to three decades, all of these loci
varied as a result of mutation, translocation or import
of DNA from unrelated neisseriae . Thus, microevolution
occurs frequently in naturally transformable bacteria .
Many variants were isolated only once or within a single
geographical location and disappeared thereafter . Other
variants achieved genetic fixation within months or a
few years . The speed with which sequence variation is
either eliminated or fixed may reflect sequential
bottlenecks associated with epidemic spread and
contrasts with the results of phylogenetic analyses from
bacteria that do not cause epidemics.
BMJ, 1997 Sep 27, 315(7111), 774 - 9
Epidemiology and clinical management of meningococcal
disease in west Gloucestershire: retrospective,
population based study; Wylie PA et al.; OBJECTIVE: To
study changes in the epidemiology and management of
meningococcal disease in one health district during a
period of high local incidence of disease . DESIGN:
Prospective case ascertainment and data collection over
14 years, with retrospective analysis of cases .
SETTING: West Gloucestershire (population 320,000) .
SUBJECTS: Residents developing meningococcal disease
between 1 January 1982 and 31 December 1995 . RESULTS:
252 cases of invasive meningococcal disease were
identified, of which 102 (40%) were officially notified
and 191 (76%) were confirmed by culture from a deep site
. The observed disease incidence of 5.6/100,000/year was
about 2.7 times the national incidence (as measured by
either statutory notifications or reference laboratory
reports) . The period 1983-90 was characterised by a
prolonged localised outbreak due to serogroup B serotype
15 sulphonamide resistant (B15R) strains . General
practitioners gave benzylpenicillin before hospital
admission to 18% of patients who presented with
meningococcal disease in the first half of the study
period and to 40% who presented in the second half . The
overall case fatality rate was 6.7% (17/252) . Four
deaths were directly or indirectly related to lumbar
puncture . Of 120 patients whose lumbar puncture yielded
meningococci, nine (8%) showed no abnormality on initial
examination . CONCLUSIONS: Neither laboratory records
nor formal notifications alone can give an accurate
estimate of the incidence of meningococcal disease .
Because of the dangers of lumbar puncture, the frequency
of misleading negative initial findings, and the advent
of new diagnostic techniques, the need for samples of
cerebrospinal fluid should be critically questioned in
each case of suspected meningococcal disease.
Pediatr Infect Dis J, 1997 Oct, 16(10), 979 - 83
Tobacco smoke as a risk factor for meningococcal
disease; Fischer M et al.; BACKGROUND: Since 1992 the US
Pacific Northwest has experienced a substantial increase
in the incidence of serogroup B meningococcal disease .
The current meningococcal polysaccharide vaccine is
poorly immunogenic in young children and does not
protect against N . meningitidis serogroup B . Defining
alternative approaches to the prevention and control of
meningococcal disease is of considerable public health
importance . METHODS: We performed a case-control study
comparing 129 patients in Oregon and southwest
Washington with 274 age- and area-matched controls . We
used conditional logistic regression analysis to
determine which exposures remained associated with
disease after adjusting for other risk factors and
confounders and calculated the proportion of disease
attributable to modifiable exposures . RESULTS: After
adjustment for all other significant exposures
identified, having a mother who smokes was the strongest
independent risk factor for invasive meningococcal
disease in children < 18 years of age {odds ratio (OR),
3.8; 95% confidence interval (CI) 1.6 to 8.9)}, with 37%
(CI 15 to 65) of all cases in this age group potentially
attributable to maternal smoking . Adult patients were
more likely than controls to have a chronic underlying
illness (OR 10.8, CI 2.7 to 43.3), passive tobacco smoke
exposure (OR 2.5, CI 0.9 to 6.9) and to smoke tobacco
(OR 2.4, CI 0.9 to 6.6) . Dose-response effects were
seen for passive smoke exposure and risk of disease in
all age groups . CONCLUSION: Tobacco smoke exposure
independently increases the risk of developing
meningococcal disease.
Biochemistry, 1997 Oct 14, 36(41), 12583 - 91
Thermodynamic analysis of the interaction between a
bactericidal antibody and a PorA epitope of Neisseria
meningitidis; van den Elsen JM et al.; An
antibody-peptide model system was used to study the
binding characteristics between a bactericidal antibody
(MN12H2) and the P1 . 16 epitope of class 1 outer
membrane protein PorA of Neisseria meningitidis by means
of a thermodynamic approach . A series of four linear
peptides and three "head-to-tail" cyclic peptides (with
ring sizes of 9, 15 and 17 amino acids) were synthesized
and evaluated as ligands . The peptides contain a
fluorescein label and the core determinant amino acid
sequence TKDTNNN (residues 180-186) of the PorA P1.16
epitope of meningococcal strain H44/76 . Thermodynamic
data of the binding of the peptide homologs of the
epitope by MN12H2 were assessed by measuring affinity
constants (Ka) over a temperature range of 4-55 degrees
C, using fluorescence spectroscopy . Curvilinear plots
of ln Ka versus T (K) revealed strong temperature
dependencies of enthalpy (DeltaH) and entropy (DeltaS) .
The Gibbs free energy change (DeltaG) was only weakly
temperature dependent . The large negative enthalpy
value indicated the importance of polar interactions in
the binding of both linear and cyclic peptides by MN12H2
. Sturtevant's analysis of the thermodynamic parameters
showed large unfavorable vibrational contributions to
the binding for all linear peptides {Sturtevant, J . M .
(1977) Proc . Natl . Acad . Sci.U.S.A . 74, 2236-2240} .
The large hydrophobic contribution compensating these
vibrational modes was partially attributed to aspecific
interaction of the fluorescein label with the antibody .
Binding of MN12H2 to conformationally restricted epitope
sequences was characterized by a dramatic reduction in
the size of unfavorable vibrational components of the
thermodynamic parameters . Substitution of individual
charged amino acids of the P1.16 epitope sequence
revealed that aspartate-182 was essential for the
binding . The pH profile observed for the MN12H2-peptide
complexes with a midpoint pH of approximately 8.5
suggests a positively charged histidine from the
antibody binding site to be involved in a charge
interaction with Asp-182 . These findings are consistent
with the results from the crystal structure of the Fab
fragment of MN12H2 in complex with a linear fluorescein-conjugated
peptide homolog of the P1.16 epitope {van den Elsen et
al . (1997) Proteins (in press)}, thereby identifying
the basis of an increased incidence of endemic disease
in England and Wales since 1981 caused by a mutant
meningococcal strain.
Clin Immunol Immunopathol, 1997 Nov, 85(2), 134 - 42
T-Cell epitope mapping the PorB protein of serogroup B
Neisseria meningitidis in B10 congenic strains of mice;
Delvig AA et al.; T-cell epitope mapping the
meningococcal serotype 15 PorB protein performed in this
study in three congenic strains of mice with B10 genetic
background revealed at least three murine T-cell
epitopes (55-72, 163-180, and 226-261), located in the
highly conserved putative transmembrane regions of
Neisserial porins . Proliferation assays with popliteal
lymph node cells derived from mice immunized with the
PorB protein or with synthetic 18-mer peptides showed
that epitope 163-180 immunized only in the H-2d
haplotype, epitope 55-72 could be presented by both H-2f
and H-2s molecules, while the 226-261 region covered by
three overlapping peptides could be efficiently
recognized in context of all three MHC class II
haplotypes studied . Inhibition experiments with
blocking I-Aalpha- and I-Ealpha-specific mAb showed that
peptide 163-180 was presented by I-Ad and peptide
244-261 was presented by both I-Af and I-As . In
addition, evidence was obtained that peptide 226-243 was
presented in context of H-2d or I-As haplotypes and
peptide 55-72 was presented in context of I-Af and I-As
loci . Finally, the Norwegian outer membrane vesicle
vaccine, but not the purified PorB protein, could recall
responses in mice immunized with synthetic peptides
corresponding to the 226-261 region . Altogether, these
results suggest that T-cell epitopes identified on the
serotype 15 PorB protein, particularly those presented
by several MHC class II molecules (e.g., 226-261), could
have important implications for the development of
meningococcal vaccines .
J Pediatr, 1997 Sep, 131(3), 398 - 404
Incidence of bacteremia in infants and children with
fever and petechiae; Mandl KD et al.; OBJECTIVE: We
determined the incidence of serious invasive bacteremia
caused by Neisseria meningitidis and other organisms in
febrile infants and children with a petechial rash .
Further, we studied the diagnostic value of laboratory
and clinical finding in these patients . STUDY DESIGN:
We conducted this prospective cohort study in the
emergency department of an urban pediatric teaching
hospital, during an 18-month period, and enrolled
consecutive patients with temperature of 38 degrees C or
higher and petechiae . Our measures included (1)
laboratory tests (leukocyte count, coagulation profile,
blood culture, and cerebrospinal fluid bacterial
culture); (2) a questionnaire requesting clinical data
including general appearance, number and location of
petechiae, and presence or absence of purpura; and (3) a
follow-up telephone survey documenting health status .
RESULTS: A total of 411 patients were enrolled, with
57.7% between 3 and 36 months of age . Eight patients
(1.9%) had bacteremia or clinical sepsis . Six had
serious invasive bacteremia: N . meningitidis (two
patients), group A streptococcus (one), or sepsis with
negative culture results (three) . Two had occult
bacteremia caused by Streptococcus pneumoniae and no
evidence of sepsis . No patient had a positive
cerebrospinal fluid culture result . None of the 357
well-appearing patients (95% confidence interval: 0.0%,
1.0%) had serious invasive bacteremia . Fifty-three
patients appeared ill, including all six with serious
invasive bacteremia . Ill appearance of the child had a
sensitivity of 1.00 (95% confidence interval: 0.60,
1.00), and a leukocyte count of 15,000 or greater, or of
less than 5000, had a sensitivity of 1.0 (95% confidence
interval: 0.53, 1.00) for detecting serious invasive
bacteremia . All children with meningococcemia had
purpura . CONCLUSIONS: Invasive bacteremia occurred less
frequently in our study than in previous series and was
identified by clinical criteria . Our data support the
treatment of selected well-appearing children with fever
and petechiae as outpatients.
Eur J Obstet Gynecol Reprod Biol, 1997 Aug, 74(2), 145 -
7
Endocervical infection in a pregnant woman caused by
Neisseria meningitidis: evidence of associated
oropharyngeal colonization of the male partner; Harriau
P et al.; A case of premature birth associated with an
endocervical infection caused by Neisseria meningitidis
is reported . Treatment of the mother with amoxycillin
eradicated the bacteria from the endocervix and avoided
newborn colonization or infection . Epidemiological
investigation identified meningococcal oropharyngeal
colonization of the male partner . The two strains were
of the same antigenic formula B:4:P1.14 and exhibited
identical rDNA restriction fragment patterns and outer
membrane protein profiles . This phenotypic and genomic
identity of strains is the first clear evidence for
cross-colonization between sexual partners.
Acta Paediatr, 1997 Sep, 86(9), 1009 - 10
Screening for complement deficiency in bacterial
meningitis; Ernst T et al.; Seventy-seven children with
bacterial meningitis were screened for complement
deficiency . Both the classical and the alternate
pathways were normal in 75 patients . Transiently
reduced total haemolytic activity of the classical
pathway was documented in a boy with meningococcal
meningitis . Total haemolytic activity of both the
classical and the alternate pathways were reduced in
another patient with pneumococcal meningitis: individual
complement components determination indicated
predominant activation of the alternate pathway.
J Acquir Immune Defic Syndr Hum Retrovirol, 1997 Aug 15,
15(5), 375 - 80
HIV-1 risk and vaccine acceptability in the Ugandan
military; Hom DL et al.; Between July and October 1993,
570 19- to 22-year-old volunteers were screened for
HIV-1, with a resulting seroprevalence rate of 18.3%
(95% CI: 14.0%, 22.6%) . A cohort of 249
HIV-1-noninfected military recruits in the Ugandan
Peoples' Defense Forces was followed prospectively for
up to 18 months to document rates of HIV-1
seroprevalence, seroconversion, and knowledge and
attitudes related to vaccine acceptability . The HIV-1
seroincidence rate was 3.56 per 100 person-years (95%
CI: 1.49, 5.62) over 309 person-years of observation .
At the 3- and 12-month visits, subjects were interviewed
on issues of acceptance and knowledge about vaccines,
including anti-HIV vaccines in particular . More than
90% believe that HIV vaccines will not cause HIV
infection, and if offered, 88% report that they would
take the vaccine if they were not already infected .
Nonvaccine prevention methods were considered less
reliable; monogamy and condom use were considered
effective by only 33.5% and 69.3% of the cohort
respectively . After completing the vaccine
acceptability questionnaire at the 12-month visit,
subjects were offered an approved polyvalent
meningococcal vaccine as an indicator of general vaccine
acceptance . All subjects reported receiving at least
one previous vaccination, and 95% willingly accepted the
meningococcal vaccination . The Ugandan military is a
stable population at substantial risk for HIV-1
infection and may be a suitable population for vaccine
efficacy trials.
Rev Prat, 1997 Sep 1, 47(13), 1428 - 32
{Febrile purpura in children}; Gillet Y et al.; The
association of fever and purpura should first suggest
the diagnosis of fulminant meningococcemia, owing to the
severity of this condition . Compromise of peripheral
circulation (cyanosis, prolonged refilling time) is
important to consider, because normal blood pressure is
usually observed at an early stage of a septic shock in
children and particularly in young infants . When this
hypothesis has been eliminated, other causes of febrile
purpura can be considered: meningococcal meningitis;
measles or other viral diseases; non infectious causes
include mechanical purpura, Schonlein-Henoch's purpura
and thrombocytopenia . In the frequent case where no
cause has been found, the diagnosis of occult
bacteriaemia should be considered, leading to parenteral
administration of antibiotic following blood and
cerebrospinal fluid cultures.
Clin Microbiol Rev, 1997 Oct, 10(4), 650 - 73
A week in the life of a travel clinic; Blair DC;
International travel has increased enormously in recent
years . With the greater movement of people have come
increased encounters with a wide variety of diseases:
malaria, dengue, cholera, typhoid fever, Ebola virus,
and many more . The need for greater scope, consistency,
and knowledgeability in pretravel health care to meet
these challenges has been met by the emergence of the
discipline of travel medicine . Travelers are well
advised to become informed of the risks they face and to
take steps to minimize those risks . After reviewing a
traveler's medical history and a detailed itinerary, a
travel medicine practitioner can offer expert advice on
behavioral modifications, immunizations, and
chemoprophylaxis regimens which will increase the
traveler's margin of safety . The issues most frequently
addressed in a travel clinic include treatment of
traveler's diarrhea, malaria chemoprophylaxis, and
immunizations, for hepatitis A, typhoid fever,
tetanus/diphtheria, influenza, pneumococcus, hepatitis
B, polio, meningococcus, measles, mumps, rubella,
varicella, and rabies . Pretravel consultation must
consider the age and underlying health problems of the
traveler, the nature of the trip (wilderness, jungle,
rural, urban, resort, or cruise), the duration of
travel, and the latest available information on the site
in terms of disease outbreaks, terrorism, and natural
calamities.
J Bacteriol, 1997 Oct, 179(20), 6400 - 7
Identification of human transferrin-binding sites within
meningococcal transferrin-binding protein B;
Renauld-Mongenie G et al.; Transferrin-binding protein B
(TbpB) from Neisseria meningitidis binds human
transferrin (hTf) at the surface of the bacterial cell
as part of the iron uptake process . To identify hTf
binding sites within the meningococcal TbpB, defined
regions of the molecule were produced in Escherichia
coli by a translational fusion expression system and the
ability of the recombinant proteins (rTbpB) to bind
peroxidase-conjugated hTf was characterized by Western
blot and dot blot assays . Both the N-terminal domain
(amino acids {aa} 2 to 351) and the C-terminal domain (aa
352 to 691) were able to bind hTf, and by a peptide spot
synthesis approach, two and five hTf binding sites were
identified in the N- and C-terminal domains,
respectively . The hTf binding activity of three rTbpB
deletion variants constructed within the central region
(aa 346 to 543) highlighted the importance of a specific
peptide (aa 377 to 394) in the ligand interaction .
Taken together, the results indicated that the N- and
C-terminal domains bound hTf approximately 10 and 1000
times less, respectively, than the full-length rTbpB (aa
2 to 691), while the central region (aa 346 to 543) had
a binding avidity in the same order of magnitude as the
C-terminal domain . In contrast with the hTf binding in
the N-terminal domain, which was mediated by
conformational epitopes, linear determinants seemed to
be involved in the hTf binding in the C-terminal domain
. The host specificity for transferrin appeared to be
mediated by the N-terminal domain of the meningococcal
rTbpB rather than the C-terminal domain, since we report
that murine Tf binds to the C-terminal domain . Antisera
raised to both N- and C-terminal domains were
bactericidal for the parent strain, indicating that both
domains are accessible at the bacterial surface . We
have thus identified hTf binding sites within each
domain of the TbpB from N . meningitidis and propose
that the N- and C-terminal domains together contribute
to the efficient binding of TbpB to hTf with their
respective affinities and specificities for determinants
of their ligand.
FEMS Immunol Med Microbiol, 1997 Sep, 19(1), 1 - 5
Reactivity of the new monoclonal antibody '22' with
meningococcal strains isolated from patients and
carriers in Greece; Tzanakaki G et al.; Previous studies
found that the majority of Neisseria meningitidis
isolates from either patients or carriers in Greece do
not react with the monoclonal antibodies used at present
in the whole-cell ELISA (WCE) for determination of
serotype and subtype antigens . A new monoclonal
antibody designated '22' produced by the National
Meningococcal Reference Laboratory in the Czech Republic
was assessed in the whole-cell ELISA with 257 non-typable
meningococcal strains from both patients (52) and
carriers (205) . The carrier strains included 34 non-typable
isolates from two immigrant populations: ethnic Greeks
who have immigrated from Russia since 1989 (19/75) and
Kurdish refugees (15/34) . Approximately 10% of the
meningococcal strains isolated from patients and 11.7%
of the carrier strains reacted with the reagent .
Although the majority of meningococcal isolates from
resident Greeks were not typable with the antibody,
11/19 (57.9%) of the carrier strains from Russian
immigrants and 4/15 (20%) of those from the Kurdish
refugees reacted with the new reagent.
Infect Immun, 1997 Oct, 65(10), 4341 - 9
Attachment of piliated, Opa- and Opc- gonococci and
meningococci to epithelial cells elicits cortical actin
rearrangements and clustering of tyrosine-phosphorylated
proteins; Merz AJ et al.; Attachment of piliated
Neisseria gonorrhoeae or Neisseria meningitidis cells to
A431, Chang, HEC-1-B, or polarized T(84) cells triggers
rearrangements of cortical microfilaments and the
accumulation of phosphotyrosine-containing proteins at
sites of bacterial contact . Actin stress fibers and the
microtubule network remain unaltered in infected cells .
The rearrangements reported here are triggered by
piliated, Opa- and Opc- strains and also by nonpiliated
gonococci (GC) that produce the invasion-associated OpaA
protein . Thus, neisserial adhesion via either of at
least two different adhesins can trigger cortical
rearrangements . In contrast, these rearrangements are
not triggered by nonadherent GC or meningococcal
strains, by heat-killed or chloramphenicol-treated GC
strains, or by Escherichia coli recombinants that adhere
to cells via GC OpaA or Opal fusion proteins, suggesting
that additional neisserial components are involved .
Immunoblotting experiments did not detect consistent
increases in the phosphorylation of specific proteins .
Possible biological implications of these Neisseria-induced
cortical rearrangements are discussed.
Infect Immun, 1997 Oct, 65(10), 4022 - 9
Complement factor C3 deposition and serum resistance in
isogenic capsule and lipooligosaccharide sialic acid
mutants of serogroup B Neisseria meningitidis; Vogel U
et al.; Serogroup B meningococci express sialic acids on
their surfaces as a modification of the
lipooligosaccharide (LOS) and as capsular material
consisting of alpha2,8-linked sialic acid homopolymers .
The aim of this study was to elucidate the impact of
each sialic acid component on the deposition of
complement factor C3 and serum resistance . For this
purpose, we used isogenic mutants deficient in capsule
expression (a polysialyltransferase mutant) or
sialylation of the LOS (a galE mutant) or both (a mutant
with a deletion of the cps gene locus) . Bactericidal
assays using 40% normal human serum (NHS) demonstrated
that both the capsule and LOS sialic acid are
indispensable for serum resistance . By immunoblotting
with monoclonal antibody MAb755 that is specific for the
C3 alpha-chain, we were able to demonstrate that C3 from
40% NHS was covalently linked to the surface structures
of meningococci as C3b and iC3b, irrespective of the
surface sialic acid compounds . However, C3b linkage was
more pronounced and occurred on a larger number of
target molecules in galE mutants with nonsialylated LOS
than in meningococci with wild-type LOS, irrespective of
the capsule phenotype . C3b deposition was caused by
both the classical pathway (CP) and the alternative
pathway of complement activation . Use of 10% NHS
revealed that at low serum concentrations, C3 deposition
occurred via the CP and was detected primarily on
nonsialylated-LOS galE mutants, irrespective of the
capsular phenotype . Accordingly, immunoglobulin M (IgM)
binding to meningococci from heat-inactivated NHS was
demonstrated only in both encapsulated and
unencapsulated galE mutants . In contrast, inhibition of
IgA binding required both encapsulation and LOS
sialylation . We conclude that serum resistance in
wild-type serogroup B meningococci can only be partly
explained by an alteration of the C3b linkage pattern,
which seems to depend primarily on the presence of
wild-type LOS, since a serum-resistant phenotype also
requires capsule expression.
FEBS Lett, 1997 Sep 8, 414(2), 409 - 13
Characterisation of the meningococcal transferrin
binding protein complex by photon correlation
spectroscopy; Boulton IC et al.; Photon correlation
spectroscopy demonstrated for the first time that
co-purified meningococcal TbpA+B form a complex in
solution . This structure bound hTf and the resultant
species underwent partial dissociation after exposure to
additional hTf or following prolonged incubation .
Purified TbpA and TbpB had similar apparent sizes but
showed distinctive size profiles suggesting that TbpA
forms a largely homogeneous population while TbpB may
produce more variable particle sizes under these
conditions.
Clin Infect Dis, 1997 Sep, 25(3), 640 - 6
Meningococcal septic shock in children: clinical and
laboratory features, outcome, and development of a
prognostic score; Kornelisse RF et al.; The clinical
characteristics of and outcome for 75 children with
meningococcal septic shock were studied . In addition, a
new prognostic scoring system was developed . The median
age of the patients was 3.2 years (range, 3 weeks to
17.9 years) . The most common phenotype of Neisseria
meningitidis was B:4:P1.4 (27%) . A mortality rate of
21% was observed . Ten (17%) of the 59 survivors had
serious sequelae . Calcium levels were significantly
lower in patients with seizures . Disseminated
intravascular coagulation occurred in 58% of the
patients who were tested . Logistic regression analysis
identified four laboratory features independently
associated with mortality: serum C-reactive protein
level, base excess, serum potassium level, and platelet
count . These features were used to develop a novel
scoring system with a predictive value for death and
survival of 71% and 90%, respectively . The outcome was
predicted correctly for 86% of the patients, which is
higher than rates previously reported for scoring
systems.
Lancet, 1997 Sep 20, 350(9081), 880 - 2
"Love's labours lost": failure to implement mass
vaccination against group A meningococcal meningitis in
sub-Saharan Africa; Robbins JB et al.; PIP: Despite the
availability of a safe, effective polysaccharide
vaccine, group A meningococcal meningitis epidemics
persist in sub-Saharan Africa . In October 1996, there
were almost 150,000 reported cases and 15,000 deaths,
the majority of which involved children . At 3 months of
age, induction of protective group A meningococcal
antibody levels requires 2 injections at least 1 month
apart . Reinjection of 5-year-old children increases
group A antibodies to long-term protective levels .
During meningitis epidemics in Nigeria, Mali, and
Rwanda, fatality was significantly reduced in areas
where scarce vaccine was administered selectively .
Although effective on an individual basis, selective
vaccination is unable to control meningitis epidemics .
In Chad, mass vaccination of the entire population
(excluding infants under 12 months) eliminated the
disease . Successful mass vaccination against group A
meningococcal epidemics also has been reported in Saudi
Arabia, China, and refugee camps in Africa . Although
cost is cited as an obstacle to routine mass vaccination
to prevent meningococcal meningitis in South Africa,
prevention is the least expensive approach to disease
control . It is recommended that the entire population
of Africa's meningitis belt receive group A
meningococcal vaccine in accordance with the recommended
age schedule in a mass vaccination program .
Pathol Biol (Paris), 1997 Apr, 45(4), 274 - 80
Neisseria meningitidis: fifteen cases of
bronchopulmonary infections associated with septicaemia;
Angelini S et al.; From 1989 to 1995, 4,053
meningococcal strains with a clinical information form
were sent to the National Reference Center for
Meningococci (NRCM) . Among these strains 569
meningococci (14.04%) were isolated from secretions of
the bronchopulmonary tract by expectoration or
fibroscopy protected or not from contamination by
microflora . Fifteen observations associated an
infection of bronchopulmonary syndrome and a
meningococcemia without any other symptoms . These
patients were in general elderly (mean = 71.3 years old)
except for two cases: one of them presented sickle cell
anemia and the other was very young (13 months) . In all
cases, there were signs of clinical and X-ray
pneumopathies . Among the fifteen cases described, eight
cases occurred during the winter, and four during the
spring . Twelve were described in countries north of the
Loire . Serogroup Y was isolated six times, serogroup B
four times and serogroup C three times . The small
quantity of cases did not permit us to study the
distribution of serotype and serosubtype . Three
patients, aged 92, 86 and 74 years old, died from the
meningococcal infection.
Proteins, 1997 Sep, 29(1), 113 - 25
Bactericidal antibody recognition of a PorA epitope of
Neisseria meningitidis: crystal structure of a Fab
fragment in complex with a fluorescein-conjugated
peptide; van den Elsen JM et al.; Class 1 outer membrane
protein PorA of Neisseria meningitidis is a vaccine
candidate against bacterial meningitis . Antibodies
against PorA are able to induce complement-mediated
bacterial killing and thereby play an important role in
protection against meningococcal disease . Bactericidal
antibodies are all directed against variable regions VR1
and VR2 of the PorA sequence, corresponding to loops 1
and 4 of a two-dimensional topology model of the porin
with eight extracellular loops . We have determined the
crystal structure to 2.6 A resolution of the Fab
fragment of bactericidal antibody MN12H2 against
meningococcal PorA in complex with a linear fluorescein-conjugated
peptide TKDTNNNL derived from the VR2 sequence of sero-subtype
P1.7,16 (residues 180-187) from meningococcal strain
H44/76 . The peptide folds deeply into the binding
cavity of the Fab molecule in a type I beta-turn, with
the minimal P1.16 epitope DTNNN virtually completely
buried . The structure reveals H-bonds and van der Waals
interactions with all minimal epitope residues and one
essential salt bridge between Asp-182 of the peptide and
His-31 of the MN12H2 light chain . The key components of
the recognition of PorA epitope P1.16 by bactericidal
antibody MN12H2 correspond well with available
thermodynamic data from binding studies . Furthermore,
they indicate the structural basis of an increased
endemic incidence of infection by group B meningococci
in England and Wales since 1981 associated with the
occurrence of an Neisseria meningitidis escape mutant
(strain-MC58) . The observed three-dimensional
conformation of the peptide provides a rationale for the
development of a synthetic peptide vaccine against
meningococcal disease.
Microb Pathog, 1997 Sep, 23(3), 139 - 55
Lipopolysaccharide heterogeneity and escape mechanisms
of Neisseria meningitidis: possible consequences for
vaccine development; Rune Andersen S et al.; We wanted
to compare the potential protective capacity of
antibodies to meningococcal lipopolysaccharides (LPS) .
The frequency of occurrence and degree of expression of
the epitopes recognized by murine monoclonal antibodies
(MAbs) to immunotypes L3,7,9 (9-2-L379) and L8 (2-1-L8)
and to the LPS inner core (216-Lc and 217-Lc), were
determined among 77 consecutive Norwegian meningococcal
patient isolates from 1995 . The immunotype L3,7,9 was
strongly expressed by 95% of the isolates, whereas L8
was weakly to moderately expressed by 9% . The inner
core epitopes, were widely distributed among the
serogroup B organisms, but were proved weakly expressed
. The bactericidal activity of the four MAbs to various
selected strains, was found to correlate positively with
the quantity of the LPS epitopes recognized by these
four MAbs in the bacteria . When tested in the serum
bactericidal assay (SBA), often a few percent of the
colonies of the inocula survived high concentrations of
the MAbs . The results indicate that escape from the
bactericidal action could be achieved through: (i)
selection of variants not expressing the LPS-epitope of
the actual MAb, (ii) a relative reduction in the density
of the LPS-epitope achieved by dilution with another LPS
structure or (iii) other factors, not yet understood .
In conclusion, antibodies to the L3,7,9 epitope seem to
be of importance for protection, whereas antibodies to
the epitopes of the LPS inner core or immunotype L8, are
not likely to offer protection alone . However, in order
to prevent escape through alteration of the LPS pattern
of the microbes, various LPS structures should probably
be present in the OMV vaccine.
Commun Dis Intell, 1997 Aug 21, 21(17), 233 - 6
Meningococcal disease in Australia; looking at the past,
thinking of the future; Patel M; In 1987 an unexpected
change in the epidemiology of meningococcal disease
began in Australia . The change was accompanied by an
outbreak of serogroup A meningococcal disease among
Aboriginal central Australians, and was followed by a
progressive rise in notifications of disease caused by
both serogroup B and C nationwide . Over the last 4
years, the notification rate has plateaued at 2.1-2.3
per 100,000 population . Virulent clonal groups of
serogroup A and C meningococci that have caused
outbreaks appear to be identical to strains that have
caused large outbreaks in other countries . We cannot
predict where and when the next outbreak will occur .
However, we can plan to respond swiftly when it does .
This report presents an overview of the observed trends,
the association between the microbiology and
epidemiology of meningococcal disease, and the relevance
of this association to outbreaks, with recommendations
for management.
FEBS Lett, 1997 Aug 18, 413(2), 364 - 70
Identification of potential ferric binding residues in
the iron-binding protein of pathogenic Neisseria
meningitidis through structure-based multiple sequence
alignments; Gorinsky B et al.; The ferric iron-binding
proteins of pathogenic Neisseria display structural and
metal-binding properties characteristic of the
transferrin family . In the absence of structural data
for the ferric iron-binding proteins, spacial folding
templates have been derived for the meningococcal
protein from complete and partial structure-based
multiple sequence alignments with structurally related
proteins . The templates have been used to identify a
number of potential iron-binding residues . These
include four residues that are identical with the iron
coordinating ligands of transferrin, but only two reside
within equivalent structural elements.
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