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+ Meningite dai Vaccini
vedi anche:
Vaccino
pneumococcico +
Siamo contro la
cosiddetta "immunizzazione" vaccinale
+
una delle
principali cause della Meningite sono i vaccini
Italy:
Ritirato
vaccino Meningitec +
info su
Meningitec
CDC e Conflitti di interesse - 1 +
CDC e Conflitti
di interesse - 2
+
CDC e Conflitti
di interesse - 3
+
Corruzione
CDC conflitti di interesse
anche per i vaccini
http://healthimpactnews.com/2014/cdcs-purchase-of-4-billion-of-vaccines-a-conflict-of-interest-in-overseeing-vaccine-safety/
Bibliografia
per i
Danni dei vaccini -
vedi anche:
http://www.greenmedinfo.com/page/vaccine-research
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
Przegl Epidemiol, 1998, 52(3),
227 - 35
{Meningococcal infections in Warsaw's district}; Dulny G et
al.; The epidemiological situation of meningococcal
meningitis in Warsaw's district in comparison to the
situation in Poland in the years 1980-1997 in discussed . In
September 1997, the local population of Zielonka--small city
in Warsaw's district, was alarmed by two meningococcal
septicaemia cases in girls attending to the same
kindergarten . Anti-epidemic measures undertaken were
described.
Epidemiol Mikrobiol Imunol, 1998 Dec, 47(4), 131 - 6
{Factors affecting Neisseria meningitidis and Neisseria
lactamica carrier state}; Krizova P et al.; Invasive
meningococcal diseases have become in the Czech Republic
since 1993 a serious epidemiological and clinical problem
due to a clonus which was not present previously: Neisseria
meningitidis C:2a:P1.2,P1.5, ET-15/37 . In 1996 a trial was
conducted focused on the problem how this altered
epidemiological and clinical situation is reflected in
carriership of Neisseria meningitidis and Neisseria
lactamica in the healthy population . Two age groups were
followed up which were most severely affected by the new
clonus of the meningococcus: 15-19 years (410 subjects) and
1-4 years (116 subjects) . The trial was implemented in
Olomouc where in 1993 the new epidemiological situation of
the incidence of the invasive meningococcal disease was so
serious that targeted vaccination was introduced . Of 116
children in the age group from 1-4 years in none Neisseria
meningitidis was detected, in 9 Neisseria lactamica was
found (7.7%) . On repeated examination of children with a
positive cultivation of Neisseria lactamica after two weeks
in none Neisseria meningitidis nor Neisseria lactamica were
found . Of 410 subjects in the age group
from 15-19 years in none Neisseria lactamica was detected
and in 35 Neisseria meningitidis (8.5%) . Examinations were
repeated after two weeks in 33 carriers: in 31 Neisseria
meningitidis was again cultivated . Analysis of factors
influencing carriership revealed in Neisseria lactamica two
factors in young children which significantly promote this
carriership: cold and close contact/kissing . A risk factor
at the limit of significance are frequent respiratory
diseases . In the carriership of Neisseria meningitidis in
15-19 year-old subjects six factors were revealed which
promote carriership . A significant risk factor is close
contact/kissing, the existence of partnership, participation
in activities of the "disco" type, living in a town, flats
in the centre of the town . Effort is a risk factor at the
limit of significance.
Nurs Stand, 1998 Oct 21-27, 13(5), 49 - 52; quiz 55-6
Meningococcal disease; Bowler S; This article discusses
meningococcal disease and outlines the role of the nurse in
treating patients who may suffer from meningitis, one of the
illnesses caused by meningococcal disease . It goes on to
discuss how nurses can support the relatives of these
patients.
Infect Immun, 1999 Feb, 67(2), 954 - 7
Role of lipopolysaccharide sialylation in serum resistance
of serogroup B and C meningococcal disease isolates; Vogel U
et al.; alpha-2,3-Sialyltransferase mutants of three
genetically and phenotypically diverse Neisseria
meningitidis strains were compared with regard to resistance
to human serum and systemic spread in the infant rat .
Lipopolysaccharide sialylation was found to be of minor
importance for the resistance of serogroup B and C
meningococcal disease isolates to complement attack.
Infect Immun, 1999 Feb, 67(2), 921 - 7
Antigen-specific T-cell responses in humans after intranasal
immunization with a meningococcal serogroup B outer membrane
vesicle vaccine; Oftung F et al.; We have studied the
ability of the Norwegian group B meningococcal outer
membrane vesicle (OMV) vaccine, when administered
intranasally without adjuvant, to induce T-cell responses in
humans . A group of 12 vaccinees was immunized with four
doses of OMVs (250 micrograms of protein/dose) at weekly
intervals, and a single booster dose was given 5 months
later . In vitro T-cell proliferation in response to the OMV
vaccine, purified PorA (class 1) protein, PorB (class 3)
protein, and one unrelated control antigen (Mycobacterium
bovis BCG) was measured by {3H}thymidine incorporation into
peripheral blood mononuclear cells obtained from the
vaccinees before and after the immunizations . The nasal OMV
immunizations induced antigen-specific T-cell responses in
the majority of the vaccinees when tested against OMVs (7 of
12) and the PorA antigen (11 of 12) . None of the vaccinees
showed a vaccine-induced T-cell response to the PorB antigen
after the initial four doses . Although some individuals
responded to all the vaccine antigens after the booster
dose, this response was not significant when the vaccinees
were analyzed as a group . We have also demonstrated that
the PorA antigen-specific T-cell responses correlated with
anti-OMV immunoglobulin A (IgA) levels in nasal secretions,
with anti-OMV IgG levels in serum, and with serum
bactericidal activity . In conclusion, we have shown that it
is possible to induce antigen-specific T-cell responses in
humans by intranasal administration of a meningococcal OMV
vaccine without adjuvant.
Schweiz Med Wochenschr, 1998 Dec 12, 128(50), 1988 - 93
{Chronic meningococcemia--a rare, but characteristic disease
picture}; Grob H et al.; Chronic meningococcaemia is a rare
clinical manifestation of invasive infection by Neisseria
meningitidis . The clinical signs and symptoms are recurrent
fever, skin rash, arthralgias and headache . This
constellation is rather typical and may enable the clinician
to establish the diagnosis . The clinical diagnosis is
confirmed by the growth of Neisseria meningitidis in the
blood culture . In addition, the clinical course under
antibiotic treatment leads to a dramatic improvement within
24-48 hours . Positive cultures may be obtained by needle
aspiration or skin biopsy . There are a few reports on
patients with deficiency of late complement components or
immunoglobulin deficiency . We report on two patients with
the typical findings of chronic meningococcaemia.
Crit Rev Microbiol, 1998, 24(4), 281 - 334
Genetic basis for biosynthesis, structure, and function of
meningococcal lipooligosaccharide (endotoxin); Kahler CM et
al.; The exclusive human pathogen Neisseria meningitidis
expresses lipooligosaccharide (LOS), an endotoxin that is
structurally distinct from the lipopolysaccharides (LPS) of
enteric Gram-negative bacilli . Differences that appear to
be biologically important occur in the composition and
attachment of acyl chains to lipid A, phosphorylation
patterns of lipid A, and the incorporation and
phosphorylation of sugar residues in the LOS inner core .
Further, unlike most enteric LPS, only two to five sugar
residues are attached to the meningococcal LOS inner core,
and there are no multiple repeating units of O-antigens . In
contrast to Escherichia coli, where the LPS biosynthesis
genes are organized as large operons, the meningococcal LOS
biosynthesis genes are organized into small operons or are
located individually in the chromosome . Some of these
genetic loci in meningococci and gonococci display
polymorphisms caused by localized chromosomal rearrangements
. One mechanism of antigenic variation of meningococci LOS
is the regulation of glycosyltransferase activity by slipped
strand mispairing of homopolymeric tracts within the 5' end
of the genes encoding these enzymes, resulting in the
addition of different sugar residues to the LOS molecule .
Meningococcal LOS is a critical virulence factor in N .
meningitidis infections and is involved in many aspects of
pathogenesis, including the colonization of the human
nasopharynx, survival after bloodstream invasion, and the
inflammation associated with the morbidity and mortality of
meningococcemia and meningitis . Meningococcal LOS, which is
a component of serogroup B meningococcal vaccines currently
in clinical trials, has been proposed as a candidate for a
new generation of meningococcal vaccines . The rapidly
expanding knowledge of the genetic basis for biosynthesis,
structure, and regulation of meningococcal LOS provides
insights into unique endotoxin structures and the precise
role of LOS in the pathogenesis of meningococcal disease.
Burns, 1998 Nov, 24(7), 680 - 2
Purpura fulminans localising to a recent burn injury;
Wharton SM et al.; The development of progressive, severe
skin changes (purpura fulminans) is a serious complication
of septicaemia, particularly meningococcal septicaemia .
Purpura fulminans almost invariably leads to some full
thickness skin loss and may lead to limb amputation . The
pathophysiology may involve microemboli, endotoxins and
direct bacterial damage to the vessels . We describe a case
of purpura fulminans, probably as a result of meningococcal
septicaemia, localising to a recent, healed burn with
complete resolution . We can find no other record of the
skin manifestations of meningococcal septicaemia localising
to a previous injury.
J Biol Chem, 1999 Jan 15, 274(3), 1495 - 501
Bactericidal antibody recognition of meningococcal PorA by
induced fit . Comparison of liganded and unliganded Fab
structures; van den Elsen J et al.; MN12H2 is a bactericidal
antibody directed against outer membrane protein PorA
epitope P1.16 of Neisseria meningitidis . Binding of MN12H2
to PorA at the meningococcal surface activates the classical
complement pathway resulting in bacterial lysis . We have
determined the crystal structure of the unliganded MN12H2
Fab fragment in two different crystal forms and compared it
with the structure of the Fab in complex with a
P1.16-derived peptide . The unliganded Fabs have elbow bend
angles of 155 degrees and 159 degrees, whereas the liganded
Fab has a more closed elbow bend of 143 degrees .
Substantial differences in quaternary and tertiary structure
of the antigen binding site are observed between the
unliganded and liganded MN12H2 Fab structures that can be
attributed to peptide binding . The variable light and heavy
chain interface of the liganded Fab is twisted by a 5
degrees rotation along an axis approximately perpendicular
to the plane of the interface . Hypervariable loops H1, H2,
and framework loop FR-H3 follow this rotation . The
hypervariable loop H3 undergoes conformational changes but
remains closely linked to hypervariable loop L1 . In
contrast with the binding site expansion seen in other Fab-peptide
structures, the MN12H2 binding site is narrowed upon peptide
binding due to the formation of a "false floor" mediated by
arginine residue 101 of the light chain . These results
indicate that PorA epitope P1.16 of N . meningitidis is
recognized by the complement-activating antibody MN12H2
through induced fit, allowing the formation of a highly
complementary immune complex.
JAMA, 1998 Dec 23-30, 280(24), 2094 - 8
Serogroup Y meningococcal disease in Chicago, 1991-1997;
Racoosin JA et al.; CONTEXT: In 1994, surveillance by the
Chicago Department of Public Health detected a growing trend
in the proportion of invasive meningococcal infections
caused by serogroup Y . OBJECTIVE: To examine the emergence
of serogroup Y meningococcal disease and compare its
clinical characteristics with those of other meningococcal
serogroups . DESIGN: Population-based retrospective review
of surveillance records; medical record review and cohort
analysis of serogroup Y vs non-serogroup Y case patients .
SETTING: Chicago, III . PARTICIPANTS: City residents with
Neisseria meningitidis isolated from a normally sterile site
from January 1, 1991, through December 31, 1997; cohort
analysis included those identified through March 31, 1996 .
MAIN OUTCOME MEASURES: Serogroup-specific incidence,
demographics, and clinical outcomes . RESULTS: We identified
214 case patients; 53 (25%) had serogroup Y . The attack
rate of serogroup Y meningococcal disease increased from
0.04 cases per 100000 in 1991 to a peak of 0.82 cases per
100000 in 1995 and subsequently decreased to 0.26 cases per
100000 and 0.34 cases per 100000 in 1996 and 1997,
respectively . Compared with patients infected by other
serogroups, patients with serogroup Y were older (median
age, 16 years vs 1 year; P = .001) and more likely to have a
chronic underlying illness (prevalence ratio, 2.3; 95%
confidence interval, 1.2-4.4) . Outcome did not differ
significantly between the 2 groups . Multilocus enzyme
electrophoresis typing of isolates from 19 case patients
identified 5 different types . We found no clustering among
the enzyme types by age, race/ethnicity, community area, or
time . CONCLUSIONS: Serogroup Y emerged as the most frequent
cause of meningococcal disease in Chicago in 1995 and
accounted for a substantial proportion of cases in 1996 and
1997 . Current data suggest that the magnitude of serogroup
Y meningococcal disease is sufficient for vaccine developers
to incorporate serogroup Y into new vaccines.
Intern Med, 1998 Nov, 37(11), 990 - 4
Adrenal hemorrhage associated with Klebsiella oxytoca
bacteremia; Hori K et al.; Septic adrenal hemorrhage is
classically caused by meningococcemia . An autopsied case is
presented of a 45-year-old man with adrenal hemorrhage due
to Klebsiella oxytoca bacteremia following placement of a
central venous catheter . He died 5 hours after developing
disseminated intravascular coagulation (DIC) . The bacterial
entry site may have been the catheter . The cause of death
was considered to be pulmonary edema due to bacteremia
rather than adrenal insufficiency due to hemorrhage . Septic
adrenal hemorrhage should be recognized as a subtype of
sepsis rather than adrenal insufficiency, and may be caused
in conditions of severe sepsis with DIC, independent of the
microorganic variety.
Eur J Clin Microbiol Infect Dis, 1998 Oct, 17(10), 690 - 4
Trend in incidence and case fatality of meningococcal
disease over 16 years in Northern Denmark; Sorensen HT et
al.; The incidence and case fatality rates of meningococcal
disease were assessed in the county of Northern Jutland,
Denmark, during the 16-year period from 1980 to 1995 . A
total of 320 patients were identified from the Meningococcal
Research Database, which comprises information from the
following sources: (i) the Department of Public Health, to
whom notification of meningococcal disease is obligatory;
(ii) the Regional Hospital Discharge Registry; and (iii) the
register of the regional department of clinical microbiology
. In order to assess prognostic indicators assessable at
admission, information was collected for each patient from
hospital records regarding contacts, symptoms and signs on
arrival, laboratory data, and course of disease . The mean
incidence was 4.3 cases per 100000 persons per year (range,
2.7-7.7) . The incidence increased slightly during the
period studied . Overall, the case fatality rate was 9.7%,
with a significant rise occurring during the period
(P=0.016) and a peak occurring in 1992 . Advanced age (> or
= 50 years), seizures, impaired consciousness, and skin
bleeding on arrival at hospital were predictors of death.
Infect Immun, 1999 Jan, 67(1), 113 - 9
Immunogenicity of intranasally administered meningococcal
native outer membrane vesicles in mice; Saunders NB et al.;
Colonization of the human nasopharyngeal region by Neisseria
meningitidis is believed to lead to natural immunity .
Although the presence of bactericidal antibody in serum has
been correlated with immunity to meningococcal disease,
mucosal immunity at the portal of entry may also play an
important role . This study was undertaken to examine in
mice the possibility of safely using native outer membrane
vesicles (NOMV) not exposed to detergent as an intranasal (i.n.)
vaccine . The mucosal and systemic responses of mice to
intranasal and intraperitoneal (i.p.) vaccination with NOMV
were compared over a range of doses from 0.1 to 20 microgram
. Intranasal vaccination of mice with NOMV induced a strong
systemic bactericidal antibody response, as well as a strong
local immunoglobulin A immune response in the lung as
determined by assay of lung lavage fluid by enzyme-linked
immunosorbent assay and lung antibody secreting cells by
enzyme-linked immunospot assay . However, 8- to
10-fold-higher doses of NOMV were required i.n . compared to
i.p . to elicit an equivalent bactericidal antibody response
in serum . Some NOMV vaccine was aspirated into the lungs of
mice during i.n . immunization and resulted in an acute
inflammatory response that peaked at 1 to 2 days
postimmunization and was cleared by day 7 . These results
indicate that i.n . delivery of meningococcal NOMV in mice
is highly effective in eliciting the production of both a
mucosal immune response and a systemic bactericidal antibody
response.
Hum Genet, 1998 Oct, 103(4), 506 - 12
The molecular basis of C6 deficiency in the western Cape,
South Africa; Hobart MJ et al.; Deficiency of the sixth
component of human complement (C6) has been reported in a
number of families from the western Cape, South Africa .
Meningococcal disease is endemic in the Cape and almost all
pedigrees of total C6 deficiency (C6Q0) have been
ascertained because of recurrent disease . We have sequenced
the expressed exons of the C6 gene from selected cases and
have found three molecular defects leading to total
deficiency: 879delG, which is the common defect in the Cape
and hitherto unreported, and 1195delC and 1936delG, which
have been previously reported in African-Americans . We also
show that the 879delG and 1195delC defects are associated
with characteristic C6/C7 region DNA marker haplotypes,
although small variations were observed . The 1936delG
defect was observed only once in the Cape, but its
associated haplotype could be deduced . The data from the
haplotypes indicate that these three molecular defects
account for the defects in all the 38 unrelated C6Q0
individuals we have studied from the Cape . We have also
observed the 879delG defect in two Dutch C6-deficient
kindreds, but the 879delG defect in the Cape probably did
not come from The Netherlands.
Scott Med J . 1998 Oct;43(5):148.
Neisseria meningitidis W135 pneumonia with sepicaemia in a
nonogenarian; Cadwgan AM et al.; Neisseria meningitidis
infection is generally considered a disease of children or
young adults, classically presenting as meningitis or
sepicaemia . This infection is rare but recognised in the
elderly . We present the case of a nonogenarian with
meningococcal pneumonia and sinusitis with bacteraemia
caused by N.meningitidis W135 a rare serogroup . We
therefore thought this unusual situation of interest and
worthwhile reporting.
Arch Pediatr, 1998 Nov, 5(11), 1232 - 5
{Chronic meningococcemia: 3 cases in the immunocompetent
child}; Grouteau E et al.; Chronic meningococcemia is a part
of extra meningeal manifestations of meningococcal disease .
Its diagnosis can be difficult because of lack of
sensitivity of blood cultures . CASE REPORT: Three cases,
concerning immunocompetent children, respectively aged of
14, 10 and 4 years are reported . The clinical course was
characterized by recurrent fever, inflammatory joint
manifestations and diffuse maculopapules secondary centered
by petechiae . Microbiological findings revealed in one case
a positive throat culture and presence of meningococcal
soluble antigens in blood and urine . In the other two
cases, diagnosis was done after done after positive blood
culture at the 7th, and 13th days of course . CONCLUSION:
The diagnosis should be considered in any children with a
prolonged, recurrent fever and cutaneous and joint
manifestations even if blood cultures remain negative . The
response to therapy by usual antimeningococcal antibiotics
is dramatic and curative while a prolonged untreated course
may be complicated by metastatic infection.
Ann Med Interne (Paris), 1998 Oct, 149(6), 332 - 9
{Vaccinations of the traveller}; Marchou B et al.; Travelers'
immunization has 2 aims: for the traveler, to prevent the
risk of contracting an endemic disease during his stay
abroad; for the community to prevent the risk of importing
an infectious agent yet unknown in the country . Travelling
offers an opportunity to update routine immunizations:
tetanus, diphtheria, poliomyelitis, hepatitis B; for young
people: measles and rubella; for elderly people: influenza .
Two vaccinations are compulsory: yellow fever for travelers
to tropical Africa and Amazonian forest; meningococcus A + C
for Mecca pilgrims . Other vaccines are recommended for
travelers to specific areas: typhoid fever, hepatitis A,
cholera in countries with poor hygiene; rabies for exposed
travelers (expatriates, trekkers...); Japanese encephalitis
for persons spending a month or longer in rural agricultural
areas during the monsoon season; tickborne encephalitis for
persons visiting forested areas of central Europe from may
to september . Yet, most of travelers' diseases such as
malaria cannot be prevented by vaccination and appropriate
preventive measures (chemoprophylaxis and protection against
insects) should be taken.
FEMS Microbiol Lett, 1998 Dec 1, 169(1), 171 - 7
Both the full-length and the N-terminal domain of the
meningococcal transferrin-binding protein B discriminate
between human iron-loaded and apo-transferrin;
Renauld-Mongenie G et al.; We have readdressed the ability
of the transferrin-binding protein B (TbpB) from Neisseria
meningitidis to discriminate between the iron-loaded and the
iron-free human transferrin (hTf) by using the BIAcore
technology, a powerful experimental technique for the
observation of direct interactions between a receptor and
its ligands, without the use of labels . Recombinant
full-length TbpB from five N . meningitidis strains were
produced and purified from Escherichia coli as fusion
proteins . They showed a preference for the binding to
iron-loaded hTf . As for the full-length molecule, we have
demonstrated that the minimal N-terminal hTf binding domain
of meningococcal TbpB from B16B6 and M982 strains was able
to discriminate between both hTf forms.
Commun Dis Rep CDR Suppl, 1998 Nov, 8(5), S1 - 12
PHLS overview of communicable diseases 1997: results of a
priority setting exercise; Rushdy A et al.; In early 1997,
the PHLS Overview of Communicable Diseases (OVCD) Committee
carried out a consultation exercise to inform the
development of PHLS priorities in communicable diseases for
the years 1997 to 1999 . The views of PHLS senior staff and
scientific committees and consultants in communicable
disease control in district health authorities were sought
by postal questionnaire, and several organisations of health
professionals were asked for their views on the initial
findings . The main findings of the exercise are summarised
in three areas of priority . Priority 1 diseases--those of
major importance to public health--included food poisoning,
meningitis, tuberculosis, sexually transmitted diseases,
vaccine preventable diseases, hospital acquired infections,
and antimicrobial resistance . Priority 2 diseases--those of
moderate importance to public health--included respiratory
syncytial virus and varicella zoster virus infections and
emerging problems such as travel associated infections .
Priority 3 diseases included those whose prevalence is
declining as a result of public health action, such as
listeriosis, and diseases of low prevalence and/or
associated morbidity . The exercise identified four areas of
possible future work for the PHLS: activities in prion
diseases, helping to tackle inequalities in health, taking a
more active approach to documenting the socioeconomic burden
of disease, and engaging more with those consulted . The
PHLS has used the results of the priority setting exercise
to guide major programme initiatives in tuberculosis,
measles, mumps, and rubella, meningococcal and pneumococcal
diseases, and in antibiotic resistance . In addition, they
have helped to shape agenda in service delivery and research
in hospital acquired infections, sexually transmitted
diseases, and gastrointestinal diseases . This exercise of
engaging corporately with key professionals in communicable
disease has paved the way for a wider engagement with
stakeholders in the setting of future priorities.
Eur J Emerg Med, 1998 Jun, 5(2), 225 - 30
Evaluation of scoring systems in acute meningococcaemia;
Hachimi-Idrissi S et al.; Patients expected to develop
life-threatening complications in acute meningococcal
infections require early recognition and appropriate
monitoring . Different prognostic scoring systems have been
developed . Three of them, chosen according to their bedside
availability, were compared with our clinical observations .
Twenty consecutive cases of proven meningococcal infection
were admitted to the paediatric intensive care unit (PICU)
of the Free University of Brussels (AZ-VUB) . Biological and
clinical features required for prognostic scoring were
evaluated as soon as possible after admission . Glasgow
meningococcal sepsis prognostic score (GMSPS), Neisseria
sepsis index (NESI) and Algren criteria were retrospectively
calculated and evaluated for their prognostic significance .
Neisseria meningitidis was cultured from blood and
cerebrospinal fluid in 11 patients and from blood in only
nine patients . The age of the patients was between 1 and 15
years (mean 4.1 years) . All patients received the same
therapy on admission . Four patients died with a multiorgan
failure within 18 hours . The three scoring systems in these
four patients predicted death . Overall, the GMSPS score,
the NESI score and the Algren criteria predicted death in
respectively 10, nine and five patients . Death was falsely
predicted in six patients by the GMSPS score, in five
patients by the NESI score and in one patient by the Algren
criteria . The Algren criteria predicted the severity of the
clinical process more accurately than did the GMSPS and NESI
scores . However, such predictability should be cautiously
used even when 100% mortality is predicted . It might be
used in decision-making in regard to the following issues:
patient transfer to tertiary centres and mode of
transportation, monitoring of patients in intensive care
units, early insertion of invasive cardiovascular monitoring
catheters and consideration of new or even experimental
therapy . However, one should be extremely cautious of
taking any therapeutically or ethical decision on the basis
of one or more of the described scoring system, since we
showed the lack of precision concerning the outcome of
paediatric patients with meningococcaemia.
Microbiology, 1998 Nov, 144 ( Pt 11), 3027 - 37
Immunization with recombinant class 1 outer-membrane protein
from Neisseria meningitidis: influence of liposomes and
adjuvants on antibody avidity, recognition of native protein
and the induction of a bactericidal immune response against
meningococci; Christodoulides M et al.; The porA gene from
Neisseria meningitidis was cloned into the pRSETA vector and
recombinant class 1 outer-membrane protein expressed at high
levels in Escherichia coli . The protein was readily
purified by affinity chromatography on a Ni2+ matrix and
used for immunization of mice with conventional AI(OH)3
adjuvant, with experimental adjuvants which have the
potential for human use, and with liposomes . The resulting
sera were analysed for the magnitude, subclass distribution
and antigenic specificity of the immune response . In
addition, surface plasmon resonance (SPR) was used to
quantify antibody avidity by analysis of the kinetics of
binding to native class 1 protein . Immunization with
conventional and experimental adjuvants induced antibodies
of low avidity that did not recognize native class 1 protein
. In contrast, immunization with recombinant protein in
liposomes induced antibodies of high avidity which
recognized native class 1 protein, as measured by their
ability to label meningococcal cells in immunofluorescence
assays and to inhibit the binding of a protective mAb .
These properties were associated with the presence in sera
of high levels of antibodies with the ability to induce
complement-mediated killing of meningococci . These data
show that liposomes containing recombinant class 1 protein
represent a potential basis of future vaccines, of defined
composition, designed for the prevention of group B
meningococcal infections.
Cytometry, 1998 Dec 1, 33(4), 406 - 13
Flow cytometric quantitation of human opsonin-dependent
phagocytosis and oxidative burst responses to meningococcal
antigens; Lehmann AK et al.; A one-step flow cytometric (FCM)
assay has been developed to quantify both opsonin- and
antigen-dependent phagocytosis and intraphagocyte oxidative
burst responses . Meningococcal outer membrane structures (OMV)
were adsorbed to fluorescent polystyrene beads, opsonized
with serum, and exposed to leukocytes . FCM parameters of
phagocytosis were evaluated in combinations with oxidative
burst indicators . Rhodamine-123 was the most sensitive
indicator and was compatible with quantitation of
phagocytosis . The phagocytosis and oxidative burst
responses induced by OMV beads were dependent on both
antigens and opsonins . Increased human opsonic responses
against OMV were induced during clinical meningococcal
disease . A dissociation was noted between phagocytosis and
oxidative burst in individual cells, indicating that
functional opsonins against OMV components may differ in
their ability to stimulate phagocytosis and oxidative burst
responses . The method facilitates evaluation of purified
bacterial structures as mediators of opsonin-dependent
phagocytosis and intracellular oxidative microbicidal
mechanisms, which is of interest in the complex process of
selecting bacterial antigens as constituents of certain
vaccines.
Clin Exp Immunol, 1998 Dec, 114(3), 362 - 9
Protection against meningococcal serogroup ACYW disease in
complement-deficient individuals vaccinated with the
tetravalent meningococcal capsular polysaccharide vaccine;
Fijen CA et al.; Individuals with properdin, C3 or late
complement component deficiency (LCCD) frequently develop
meningococcal disease . Vaccination of these persons has
been recommended, although reports on efficacy are scarce
and not conclusive . We immunized 53 complement-deficient
persons, of whom 19 had properdin deficiency, seven a C3
deficiency syndrome and 27 had LCCD with the tetravalent (ACYW)
meningococcal capsular polysaccharide vaccine . Serological
studies were performed in 43 of them . As controls 25
non-complement-deficient relatives of the
complement-deficient vaccinees and 21 healthy non-related
controls were vaccinated . Post-vaccination,
complement-deficient individuals and controls developed a
significant immunoglobulin-specific antibody response to
capsular polysaccharides group A, C, Y, W135, but a great
individual variation was noticed . Also, the proportion of
vaccinees of the various vaccinated groups with a
significant increase in bactericidal titre (assayed with
heterologous complement) was similar . Opsonization of
meningococci A and W135 with sera of the 20 LCCD individuals
yielded in 11 (55%) and eight (40%) sera a significant
increase of phagocytic activity after vaccination,
respectively . Despite vaccination, four
complement-deficient patients experienced six episodes of
meningococcal disease in the 6 years post-vaccination . Four
episodes were due to serogroup B, not included in the
vaccine . Despite good response to serogroup Y upon
vaccination, disease due to serogroup Y occurred in two
C8beta-deficient patients, 3.5 and 5 years post-vaccination
. These results support the recommendation to vaccinate
complement-deficient individuals and to revaccinate them
every 3 years.
Clin Exp Immunol, 1998 Dec, 114(3), 355 - 61
C7 deficiency in an Irish family: a deletion defect which is
predominant in the Irish; O'Hara AM et al.; Human
deficiencies of terminal complement components are known to
be associated with increased susceptibility to Neisseria
meningitidis infection . Polymorphic DNA marker studies in
complement deficient investigations allow identification of
haplotypes associated with the deficiency and enable the
possible identification of heterozygote carriers of the
defect . We report studies of an Irish family in which the
index case had suffered recurrent meningococcal disease and
was found to be deficient in the seventh component of
complement (C7) . The availability of all family members
enabled us to determine the segregating haplotypes . The
defects in the family segregated with two very closely
related C6 and C7 DNA haplotypes, one of which is known to
be associated with the large Irish C7 DNA deletion defect .
The index case and two C7 deficient siblings were found to
be homozygous for this defect, a deletion that spans approx
. 6.8 kbp and encompasses exons 7 and 8 . The deletion
defect of exons 7 and 8 of C7 has been found in homozygous
form in another C7 deficient Irish individual, and is
present in heterozygous form in C7 deficient members of a
third Irish family . Therefore, this deletion defect occurs
in five of the six deficient chromosomes of these three
unrelated Irish families, raising the interesting question
of how prevalent this defect may be within the Irish
community.
Commun Dis Rep CDR Wkly, 1998 Nov, 8 Suppl 5, S1 - 12
PHLS overview of communicable diseases 1997: results of a
priority setting exercise; Rushdy A et al.; In early 1997,
the PHLS Overview of Communicable Diseases (OVCD) Committee
carried out a consultation exercise to inform the
development of PHLS priorities in communicable diseases for
the years 1997 to 1999 . The views of PHLS senior staff and
scientific committees and consultants in communicable
disease control in district health authorities were sought
by postal questionnaire, and several organisations of health
professionals were asked for their views on the initial
findings . The main findings of the exercise are summarised
in three areas of priority . Priority 1 diseases-those of
major importance to public health-included food poisoning,
meningitis, tuberculosis, sexually transmitted diseases,
vaccine preventable diseases, hospital acquired infections,
and antimicrobial resistance . Priority 2 diseases-those of
moderate importance to public health-included respiratory
syncytial virus and varicella zoster virus infections and
emerging problems such as travel associated infections .
Priority 3 diseases included those whose prevalence is
declining as a result of public health action, such as
listeriosis, and diseases of low prevalence and/or
associated morbidity . The exercise identified four areas of
possible future work for the PHLS: activities in prion
diseases, helping to tackle inequalities in health, taking a
more active approach to documenting the socioeconomic burden
of diseases, and engaging more with those consulted . The
PHLS has used the results of the priority setting exercise
to guide major programme initiatives in tuberculosis,
measles, mumps, and rubella, meningococcal and pneumococcal
diseases, and in antibiotic resistance . In addition, they
have helped to shape agenda in service delivery and research
in hospital acquired infections, sexually transmitted
diseases, and gastrointestinal diseases . This exercise of
engaging corporately with key professionals in communicable
disease has paved the way for a wider engagement with
stakeholders in the setting of future priorities.
Eur J Pediatr, 1998 Nov, 157(11), 869 - 80
Pathophysiology of meningococcal sepsis in children; de
Kleijn ED et al.; Septic shock with purpura is a syndrome
frequently diagnosed in children and predominantly caused by
Neisseria meningitidis . Despite improvements in management
and therapy the mortality and morbidity in these patients
are still high . During the last few years much effort has
been put into understanding of the systemic host response
during this acute infectious disease . This host response
can be divided into the process of recognition of endotoxin,
the cascade of pro- and counter inflammatory mediators, the
endothelial damage resulting in capillary leakage and
inappropriate vascular tone, and the procoagulant state .
CONCLUSION: This paper reviews the recent insights in the
pathophysiology of the host response and their possible
consequences for novel therapies in meningococcal sepsis.
JAMA, 1998 Nov 18, 280(19), 1685 - 9
Induction of immunologic memory by conjugated vs plain
meningococcal C polysaccharide vaccine in toddlers: a
randomized controlled trial; MacDonald NE et al.; CONTEXT:
Meningococcal polysaccharide vaccines are not used routinely
in infants and toddlers, the groups at highest risk of
invasive disease, because of poor immunologic responses to
the Neisseria meningitidis serogroup C polysaccharide in
these age groups . Meningococcal C conjugate vaccines offer
the prospect of circumventing this problem . OBJECTIVE: To
assess the immunogenicity and the induction of immunologic
memory in toddlers by meningococcal C conjugate vaccine .
DESIGN: A multicenter, randomized, observer-blinded
controlled trial . SETTING: Urban and suburban family
medicine or pediatric practices . PARTICIPANTS: Two hundred
eleven healthy toddlers aged 15 to 23 months . INTERVENTION:
Two injections at 2 months apart of meningococcal C
conjugate (group 1, n = 69), plain meningococcal
polysaccharide (group 2, n = 72), or hepatitis B virus
vaccine (group 3, n = 70) . All toddlers received a
follow-up dose of plain meningococcal polysaccharide vaccine
12 months later . MAIN OUTCOME MEASURES: IgG meningococcal C
anticapsular antibody concentrations determined by
enzyme-linked immunosorbent assay and complement-mediated
bactericidal antibody . RESULTS: In group 1, the magnitude
of the IgG response to meningococcal C conjugate vaccine was
more than 4-fold higher after dose 1 and more than 10-fold
higher after dose 2 compared with meningococcal
polysaccharide vaccine (group 2) (P<.001) . Higher titers
persisted in the meningococcal C conjugate group for at
least 12 months (P<.001) . Group 1, primed with
meningococcal C conjugate, had 25-fold higher IgG responses
to the meningococcal polysaccharide 1-year booster dose than
the controls who had received hepatitis B virus vaccine
initially and were given meningococcal polysaccharide
vaccine 1 year later for the first time (P<.001) . In
contrast, group 2, primed with meningococcal polysaccharide,
had a 2-fold lower response to the 1-year booster
meningococcal polysaccharide dose than the hepatitis B virus
control group (P = .006) . Serum bactericidal responses
paralleled the enzyme-linked immunosorbent assay responses .
CONCLUSIONS: Immunization of toddlers with meningococcal C
conjugate vaccine induces high titers of anticapsular and
bactericidal antibody . Furthermore, this vaccine induces
immunologic memory to meningococcal C polysaccharide . In
contrast, meningococcal polysaccharide vaccine is less
immunogenic than the conjugate vaccine and also induces a
hyporesponsive state that persists for at least 12 months.
Infect Immun, 1998 Dec, 66(12), 5939 - 47
The (alpha2-->8)-linked polysialic acid capsule and
lipooligosaccharide structure both contribute to the ability
of serogroup B Neisseria meningitidis to resist the
bactericidal activity of normal human serum; Kahler CM et
al.; The molecular basis for the resistance of serogroup B
Neisseria meningitidis to the bactericidal activity of
normal human sera (NHS) was examined with a NHS-resistant,
invasive serogroup B meningococcal isolate and genetically
and structurally defined capsule-, lipooligosaccharide
(LOS)-, and sialylation-altered mutants of the wild-type
strain . Expression of the (alpha2-->8)-linked polysialic
acid serogroup B capsule was essential for meningococcal
resistance to NHS . The very NHS-sensitive phenotype of
acapsular mutants (99.9 to 100% killed in 10, 25, and 50%
NHS) was not rescued by complete LOS sialylation or changes
in LOS structure . However, expression of the capsule was
necessary but not sufficient for a fully NHS-resistant
phenotype . In an encapsulated background, loss of LOS
sialylation by interrupting the alpha2,3 sialyltransferase
gene, lst, increased sensitivity to 50% NHS . In contrast,
replacement of the lacto-N-neotetraose alpha-chain
(Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) with glucose
extensions (GlcN) in a galE mutant resulted in a strain
resistant to killing by 50% NHS at all time points .
Encapsulated meningococci expressing a
Hep2(GlcNAc)-->KDO2-->lipid A LOS without an alpha-chain
demonstrated enhanced sensitivity to 50% NHS (98% killed at
30 min) mediated through the antibody-dependent classical
complement pathway . Encapsulated LOS mutants expressing
truncated Hep2-->KDO2-->lipid A and KDO2-->lipid A
structures were also sensitive to 50% NHS (98 to 100% killed
at 30 min) but, unlike the wild-type strain and mutants with
larger oligosaccharide structures, they were killed by
hypogammaglobulinemic sera . These data indicate that
encapsulation is essential but that the LOS structure
contributes to the ability of serogroup B N . meningitidis
to resist the bactericidal activity of NHS.
Mol Microbiol, 1998 Nov, 30(3), 647 - 56
A gonococcal porA pseudogene: implications for understanding
the evolution and pathogenicity of Neisseria gonorrhoeae;
Feavers IM et al.; Members of the genus Neisseria, including
the human pathogens Neisseria meningitidis and Neisseria
gonorrhoeae, express at least one member of a family of
related porins . N . meningitidis is the only species known
to express a second porin, the meningococcal serosubtyping
antigen PorA, the most divergent member of this family .
Unexpectedly, a porA gene was identified in the gonococcal
genome . Both the gonococcal and meningococcal porA loci
were adjacent to a homologue of the Escherichia coli greA
gene, although the IS1106 element downstream of porA in some
meningococci was absent in the gonococcus . Almost identical
porA loci were present in four unrelated gonococcal isolates
and clinical specimens from patients with gonorrhoea . Lack
of PorA expression in the gonococcus resulted from mutations
in the promoter region, which prevented transcription, and
frameshift mutations in the coding region of the porA gene .
Hybridization and amplification experiments, showing the
absence of a porA gene in seven other Neisseria species,
suggested that porA was acquired by a common ancestor of the
gonococcus and meningococcus but inactivated in the
gonococcus on speciation . This implies that, while
advantageous during colonization of the upper respiratory
tract, this protein has no function in, or hinders,
colonization of the urogenital tract.
J Trop Pediatr, 1998 Oct, 44(5), 263 - 5
Changing patterns of antibiotic sensitivity and resistance
during an outbreak of meningococcal infection in Jos,
Nigeria; Angyo IA et al.; Isolates of Neisseria meningitidis
from blood and cerebrospinal fluid (CSF) of 87 children
admitted to the emergency paediatric unit (EPU) at the Jos
University Teaching Hospital (JUTH) during an outbreak of
meningococcal infection (between February and April 1996)
were tested against the commonly used antibiotics in an
attempt to determine the sensitivity and resistance pattern
. There were 11 (15.1 per cent) positive for N .
meningitidis out of 73 blood cultures and 61 (70 per cent)
positive out of 87 CSF cultures . Seventy-seven and
thirty-eight per cent respectively of the CSF isolates were
resistant to benzylpenicillin and ampicillin . Sensitivity
to chloramphenicol and erythromycin was 97 and 95 per cent,
respectively . Out of the 11 positive blood cultures, 82 and
27 per cent were resistant to benzylpenicillin and
ampicillin, respectively, while all the isolates (100 per
cent) were sensitive to chloramphenicol and erythromycin .
It is concluded that in view of the high level of resistance
of the meningococci to benzylpenicillin in our environment,
this drug should no longer be the drug of choice for the
empirical and initial treatment of meningococcal infection .
We recommend that chloramphenicol be the drug of choice for
the empirical and initial treatment of meningococcal
infection in our environment.
J Med Microbiol, 1998 Nov, 47(11), 993 - 8
Identification of nasopharyngeal carriage of an outbreak
strain of Neisseria meningitidis by pulsed-field gel
electrophoresis versus phenotypic methods; Bevanger L et
al.; The clustering of four cases of meningococcal disease
during a 3-month period in a small community with 2233
inhabitants prompted an interventional carrier survey in
persons < 19 years old and in family members of the patients
. The aims of the survey were to identify the nasopharyngeal
carriers and the carriage rate of the outbreak strain, to
offer chemoprophylaxis to those carrying the outbreak
strain, and to study the discriminatory power of phenotypic
methods versus pulsed-field gel electrophoresis (PFGE) on
carrier isolates during an outbreak . A high percentage of
the population in the age group 0-19 years (73.7%)
participated in the study . Among the 469 samples collected
in this age group, meningococci were grown from 43 (9.2%) .
The highest carriage rates were in the age group 18-19 years
(36.4%) . With a provisional definition of the outbreak
strain (group B or non-groupable Neisseria meningitidis with
reduced sulphonamide sensitivity), six carriers were
identified . All were treated with a single dose of
ofloxacin . Four of these persons (0.76% of all tested) were
later shown to have harboured the outbreak strain when
analysed by PFGE . Three of them were epidemiologically
closely related to one of the index cases . Serogrouping
alone is not sufficient for the identification of an
epidemic strain of N . meningitidis . Complete concordance
of type and subtype antigens correctly identified the
outbreak strain in this study . PFGE is well suited for the
identification of an outbreak strain of N . meningitidis
versus non-epidemic strains in tonsillo-pharyngeal
specimens.
Clin Exp Immunol, 1998 Nov, 114(2), 215 - 9
Endotoxin release and cytokine production in acute and
chronic meningococcaemia; Prins JM et al.; Chronic
meningococcaemia is a relatively benign manifestation of
meningococcal disease . Whether bacterial virulence factors
are responsible for this benign course has not been studied
. We compared the in vitro endotoxin-liberating ability and
cytokine-inducing potential of 31 Neisseria meninigitidis
isolates obtained from children with acute septic shock with
that of nine isolates obtained from patients with chronic
meningococcaemia and 12 isolates obtained from carriers with
respiratory symptoms . The median endotoxin level released
in vitro after 3 h of incubation was significantly higher
for isolates causing septic shock compared with isolates
from the other two groups (P=0.01 and 0.02, Mann-Whitney
test) . This was not explained by differences in bacterial
growth rate in vitro . The median IL-6 levels in whole blood
ex vivo after 4 h of incubation were also significantly
lower for isolates causing chronic meningococcaemia (P=0.04,
Mann-Whitney test) . The endotoxin and cytokine levels
measured on admission in the 31 children with acute
meningococcal septic shock showed a 1000-fold variation . No
relationship was established between the amount of endotoxin
released by the causative microorganisms in vitro and the
endotoxin or cytokine levels in the corresponding 31
children . These results suggest a diminished bacterial
virulence for isolates causing chronic meningococcaemia .
However, other factors than the endotoxin-releasing
potential of the microorganism involved are responsible for
the wide variation in endotoxin and therefore cytokine
levels in patients with acute meningococcal septic shock.
J Immunol, 1998 Nov 15, 161(10), 5525 - 33
IL-12 enhances antibody responses to T-independent
polysaccharide vaccines in the absence of T and NK cells;
Buchanan RM et al.; Polysaccharide vaccines to encapsulated
bacteria such as Neisseria meningitidis and Streptococcus
pneumoniae are weakly immunogenic due to their T-independent
(TI) nature . Even when converted to T-dependent forms
through conjugation to foreign proteins, polysaccharides
induce responses that are deficient in many respects, such
as induction of murine IgG2a Ab, the isotype that mediates
optimal complement fixation and opsonization . We now show
that IL-12 treatment of mice induces significantly increased
levels of IgG2a Ab to the model TI-2 Ag, DNP-Ficoll, and to
vaccines composed of polysaccharides from pneumococci and
meningococci . Use of immunodeficient mice lacking T cells
and/or NK cells demonstrated that such cells were not
responsible for the observed Ab enhancement . Furthermore,
the use of IFN-gamma knockout mice showed that stimulation
of TI-2 Ab responses by IL-12 was only partially dependent
on IFN-gamma . The ability of IL-12 to dramatically enhance
TI Ab responses suggests that IL-12 will be useful as a
powerful vaccine adjuvant to induce protective immune
responses against encapsulated pathogens.
Cas Lek Cesk, 1998 Oct 5, 137(19), 598 - 600
{Association of class I HLA antigens with invasive
meningococcal disease}; Holub M et al.; BACKGROUND: The
majority of meningococcal infections are characterized by
nasopharyngeal carriership . In some patients invasive
disease with a mild course develops, while some cases have a
lethal outcome . The reasons of this wide variation range
are not clear . The objective of the present work was to
assess whether the development of invasive meningococcal
disease or its prognosis are associated with HLA class I .
METHODS AND RESULTS: The group of patients was formed by 40
patients (29 females, 11 males, mean age 16 years, range 8
months to 52 years) . In 28 patients the disease was caused
by N . meningitidis group C, in 9 cases group B, in three
cases the serotype was not assessed . The etiology was
confirmed by cultivation or latex agglutination .
Twenty-three patients had a mild course of the disease, 8 a
medium severe one, 9 patients a severe clinical course
(score according to Stiehme, Damrosch and Rosenblat) . The
patients were compared with 227 non-related blood donors
(114 women, 113 men, 18 to 50 years old) . In patients and
controls 24 lymphocytic HLA antigens class I were identified
as to type . Typing was done using the standard
microlymphocytotoxic test in the NIH modification . The
results were processed by statistical methods using Fisher's
exact test and the 2 x 2 test with Yates correction . In
patients with a mild course HLA antigens B7 and B12
predominate (p = 0.03; p = 0.02), in medium severe cases
antigen A11 (p = 0.03), in patients with the most severe
course antigen A9 (p = 0.04) . In invasive infections caused
by N . meningitidis serotype B antigen B17 predominates (p =
0.05) . CONCLUSIONS: The severity of meningococcal invasive
infections is associated with HLA class I . Invasive disease
caused by N . meningitidis serotype B are more likely to
occur in carriers of HLA B17 . No relationship was found
between HLA class I and invasive disease caused by N .
meningitidis regardless of serotype and with serotype C.
J Clin Microbiol, 1998 Dec, 36(12), 3680 - 2
Heterogeneity of the PorB protein in serotype 22 Neisseria
meningitidis; Urwin R et al.; The genetic diversity of porB
genes from meningococcal isolates characterized as serotype
22 was investigated by gene sequencing . This procedure
identified seven distinct porB sequences, demonstrating
variation in the PorB protein recognized by the serotype 22
monoclonal antibody . This is consistent with the genetic
heterogeneity of serotype 22 meningococci reported
previously.
J Travel Med, 1994 Jun 1, 1(2), 72 - 78
Inadequacies in Health Recommendations Provided for
International Travelers by North American Travel Health
Advisors; Keystone JS et al.; The rise of international
travel has increased the need for more, improved travel
advice from physicians and public health facilities . The
quality of the health information given has not been
examined on a large-scale basis by many studies, however .
Surveys in Canada, Switzerland, and the United States, for
example, report that only 20% to 50% of practitioners could
give accurate information regarding immunization and
prophylaxis about travel-related disease . Anonymous surveys
were sent to 1165 American and 96 Canadian public health
units and travel clinics . Using five scenarios on travel to
developing countries, each source was asked to complete a
standardized form giving their recommendations for
immunization, antimalarials, travelers' diarrhea, and other
travel issues . Of the American respondents, 60% were
physicians equally distributed among private practice,
university, and corporate clinics; nurses comprised 75% of
the Canadian respondents, primarily from public health
clinics . The number of travelers counseled per year ranged
from 3 to 40,000 (American mean, 448; Canadian mean, 2180) .
Depending on the scenario, 20 to 75% of the immunization
groups recommended were inadequate or inappropriate: most
frequently, lack of tetanus/polio boosters; indiscriminant
use of yellow fever/cholera vaccines; haphazard advice about
meningococcal, rabies, and typhoid vaccines; and a lack of
consideration of measles in young adults . Of the
antimalarial recommendations given, 20 to 60% were
incorrect, including prescribing medication for nonrisk
areas, failure to recognize chloroquine-resistant areas, and
failure to understand the use of, or contraindications to,
mefloquine . Frequently, acclimatization, altitude sickness,
sunscreens, and safe-sex issues were omitted . The
prevention and treatment of travelers' diarrhea were
adequately covered, however . Pre-travel advice given by
North American health advisors shows a considerable
variability in the accuracy and extent necessary for
effective travel disease prevention and treatment . Despite
the growing efforts to further educate those responsible,
higher quality of health advice needs to become a priority.
J Travel Med, 1994 Mar 1, 1(1), 4 - 7
Meningococcal Disease in Travelers: Vaccination
Recommendations; Koch S et al.; The object of the study was
to determine the incidence rate of meningococcal disease in
travelers originating in industrialized countries and
visiting developing countries . Subjects were
intercontinental travelers with meningococcal diseases
acquired from 1986 to 1989 . Health authorities in 108
countries were contacted; data obtained by postal survey
were analyzed . The 56 replying health authorities reported
13 cases of meningococcal disease in tourist or business
persons as well as 40 primary and 26 secondary cases in
pilgrims in Mecca . The majority of cases were due to
serogroup A . The case fatality rate in both groups of
patients slightly exceeded 20% . Among the tourists and
business persons, several patients had stayed in hotels; in
several the onset of symptoms occurred during the flight
home . The incidence rate per month of stay was estimated to
be 0.4 per million travelers in this group, but 2000 per
million in pilgrims to Mecca . Vaccination of pilgrims to
Mecca is highly recommended, presently even compulsory . For
the usual traveler to endemic countries, the risk of
infection abroad seems not to exceed the one at home, thus
vaccination may be limited to high-risk groups, such as
trekkers.
Intensive Crit Care Nurs, 1998 Apr, 14(2), 91 - 5
Nursing perspectives in meningococcal disease; Moore E et
al.; Meningococcal sepsis is a potentially life threatening
disease . Recent advances have led towards increased
emphasis being placed on early identification and prompt
aggressive management of these patients . This article
outlines the disease pathology, describing a case study to
illustrate the management and nursing care of a child with
meningococcal sepsis . Current therapies are also discussed.
J Bacteriol, 1998 Nov, 180(22), 6043 - 7
Transport of intact porphyrin by HpuAB, the
hemoglobin-haptoglobin utilization system of Neisseria
meningitidis; Lewis LA et al.; The meningococcal hemA gene
was cloned and used to construct a porphyrin biosynthesis
mutant . An analysis of the hemA mutant indicated that
meningococci can transport intact porphyrin from heme (Hm),
hemoglobin (Hb), and Hb-haptoglobin (Hp) . By constructing a
HemA- HpuAB- double mutant, we demonstrated that HpuAB is
required for the transport of porphyrin from Hb and Hb-Hp.
Rev Esp Salud Publica, 1998 Jul-Aug, 72(4), 365 - 74
{Seroprevalence of bactericidal anti-meningococcal
antibodies in Cantabria 10 months following a vaccination
campaign}; Gonzalez de Aledo Linos A et al.; BACKGROUND: The
Self Governing Region of Cantabria within the state of Spain
has a population of 541,885, of which 107,787 individuals
are aged from 18 months to 19 years . A vaccination campaign
against meningitis was conducted in this Region in February
and March, 1997 . It was directed at children from the age
of 18 months up to 19 years old, and included all municipal
areas, achieving a coverage of more than 95% . In the
following 12 months the efficacy achieved by the vaccination
was 95.68% for all age groups . To help decide on the need
for re-vaccination, a study of the prevalence in serum of
bactericide antibodies in the vaccinated population was
carried out . METHODS: In December 1997 blood samples from
414 vaccinated children were analysed, obtained at random in
opportunist sampling in First-Aid Centres and Public
Hospitals within this Region, as well as from children in
public kindergartens run by the General Board of Social
Well-Being in Cantabria . The number of bactericide
antibodies was analysed in the National Centre for
Microbiology, and the level of "vaccination effect" was set
at a dilution of 1/8 . RESULTS: The following percentages of
titres > or = 1/8 were obtained (the age groups of school
pupils are shown in brackets): 0% (18-24 months old), 4%
(1.5-4 years old), 7.1% (1.5 to 6 years old), 51.3% (6 to 12
years old) . Due to the fact that the definition of the
"vaccine effect" was artificially set at a dilution of 1/8,
while other studies set it at a dilution of 1/4, in 287
serum samples with a result of < 1/8 the bactericide assay
was repeated with a dilution of 1/4, with the result that
286 (99.6%) were negative . I.e., the final result does not
vary if we set the cut-off point at 1/4 instead of 1/8 . No
significant differences were found due to whether or not the
samples came from children in municipalities where there had
been cases of meningitis C . CONCLUSIONS: Bactericide
activity is very low in those children aged less than 4-6
years old, and is less than has been published, although it
is greater above this age . This contrasts with the
excellent clinical-epidemiological results, as there was no
case amongst the least serologically "protected" population,
in spite of the fact that meningococcus C remains in
circulation in Cantabria, within the population that was not
targeted by the campaign.
Rev Cubana Med Trop, 1995, 47(2), 108 - 12
{The seasonality of meningococcal disease in infants less
than 1 year old . Cuba, 1983-1990}; Rico Cordeiro O et al.;
Children less than one year old behave as the group with the
highest incidence of meningococcal disease during all the
epidemic period in the past '80s decade in Cuba . There were
used chronological series of monthly incidence rates between
1983 and 1990, in order to identify the behavior of
seasonality, taking into account the clinical form and the
insert of years 1989 and 1990 in the series: in both of them
a massive antimeningococcal vaccination campaign took place
. It is evident that seasonality has a different behavior in
accordance with the clinical form: it is like the countries
from the northern hemisphere with a moderate climate for the
meningoencephalitis, and like the countries of the southern
hemisphere with a warm climate for the meningococcal
syndrome . Months of the rainy period have the lowest
seasonal index . Modifications of these seasonal patterns
are not found after executing the vaccination.
Rev Cubana Med Trop, 1995, 47(1), 59 - 64
{The post-licensing efficacy of VA-MENGOC-BC in children
under 6 in HolguÃn, Cuba . The first year of observation};
Rico Cordeiro O et al.; The assessment of the
after-licensing efficacy of the Cuban vaccine VA-MENGOC-BC
was performed one year after the mass immunization campaign
was completed in children under 6 years of age in the
Province of Holguin which had the second highest incidence
rate of meningococcal disease during 1988 in Cuba . In the
design of the study the following aspects were taking into
account: case definition; case detection, determination of
the state of vaccination, and comparability of exposure .
The utilization of 2 case definitions with different
sensitivity and specificity is introduced within the
methodology, as well as 2 estimation methods . Incidence
rates from exposed and nonexposed subjects, as well as the
ratio of cases and of the vaccinated population are used .
The impact of this prophylactic intervention was determined
by the estimation of the percentual preventive population
fraction . Among outstanding results, the high efficacy of
more than 98% found in both variants of case definition is
to be mentioned . It is evidenced that the effect of the
vaccine accounts for more than 80% of the observed case
reduction . Such reduction in the number of cases was
obtained without changing diagnostic criteria since the
isolation of the agents was hept at levels similar to the
ones from previous years.
Commun Dis Intell, 1998 Oct 1, 22(10), 205 - 11
Annual report of the Australian Meningococcal Surveillance
Programme, 1997; Age-related immunogenicity of meningococcal
polysaccharide vaccine in aboriginal children and
adolescents living in a Northern Manitoba reserve community;
Department of Medical Microbiology, University of Manitoba,
Canada . blaw@ms.umanitoba.ca
OBJECTIVE: To determine the total and functional serogroup C
antibody response to a quadrivalent meningococcal
polysaccharide vaccine in a group of aboriginal infants,
children and adolescents . A secondary objective was to
determine their prevalence of meningococcal carriage .
DESIGN: Open prospective, before and after intervention
study . SUBJECTS: Aboriginal children ages 0.5 to 19.9
years, living in a single Northern community and eligible
for a public health immunization campaign conducted in all
Manitoba native reserve communities to control a
meningococcal serogroup C, electrophoretic type (ET) 15
outbreak . No outbreak cases had occurred in the community
at the time of the study . METHODS: Total serogroup C
capsular polysaccharide antibody (CPA) and functional
bactericidal antibody (BA) responses were measured by
enzyme-linked immunosorbent assay and bactericidal assay,
respectively . RESULTS: Neisseria meningitidis was recovered
from the oropharynx of 13 (5.2%) of 249 aboriginal children
including 4 (1.6%) serogroup C isolates, all with the
designation C:2a:P1.2,5 ET15 . Paired sera from 152 children
were available for assay . For CPA the geometric mean
concentrations and proportions with > or =2 microg/ml before
and after immunization were 0.69, 18% and 12.3, 96%,
respectively . A significant increase in serum CPA was
achieved by children of all ages, with the greatest response
occurring after age 11 years . Among infants < lyear old 89%
achieved concentrations of > or =2 microg/ml . For BA the
pre- and post-vaccine geometric mean titers were 1.02 and
45.9 . The response was significantly associated with age .
BA titers > or =1:8 were present, before and after
immunization, respectively, in 0 and 0% of infants <1 year
old, 0 and 20% of 1- to 1.4-year-olds, 0 and 50% of 1.5- to
1.9-year-olds and 1 and 100% of > or =2-year-olds .
CONCLUSION: The age-related total and functional group C
meningococcal antibody response after quadrivalent
polysaccharide vaccine among aboriginals is similar to that
reported for Caucasian children . After age 2 all children
made excellent CPA and BA responses . In the younger age
groups the BA response was blunted but 82 to 95% achieved
CPA titers of > or =2 microg/ml.
Pediatr Infect Dis J, 1998 Oct, 17(10), 855 - 9
Cerebrospinal fluid pleocytosis and prognosis in invasive
meningococcal disease in children; Malley R et al.;
BACKGROUND: The absence of cerebrospinal fluid (CSF)
pleocytosis in invasive meningococcal disease (IMD) has been
associated with an increased risk of death . It is unknown
whether patients who lack a cellular response to central
nervous system (CNS) infection are at the same risk of
adverse outcome as patients who lack CNS infection .
OBJECTIVES: To determine the frequency of presentation and
outcome of three groups of children with IMD: Group 1,
children with CSF pleocytosis; Group 2, children without CSF
pleocytosis and with negative CSF cultures (bacteremia
alone); and Group 3, children without CSF pleocytosis but
with positive CSF cultures (CNS infection without CSF
pleocytosis) . METHODS: We reviewed the medical records of
children with IMD at four pediatric referral hospitals
between 1985 and 1996 . Clinical and laboratory indices and
severe adverse outcomes (defined as death or limb loss) were
compared in the three groups . Multivariable logistic
regression analysis was performed to determine whether CNS
infection without CSF pleocytosis was independently
associated with adverse outcome in IMD . RESULTS: Three
hundred seventy-seven children with IMD were identified .
Eighty-six patients were excluded because their CSF analysis
either was not done or was unevaluable; of these patients 22
(25.6%) had an adverse outcome . Of the 291 evaluable
patients 204 (70.1%) had CSF pleocytosis, 52 (17.9%) had
bacteremia alone and 35 (12.0%) had CNS infection without
CSF pleocytosis . Patients with CNS infection without CSF
pleocytosis had significantly lower white blood cell and
platelet counts and more coagulopathy than patients with
bacteremia alone (P < or = 0.05) or patients with CSF
pleocytosis (P < or = 0.01) . The frequency of adverse
outcome was 40% for patients with CNS infection without CSF
pleocytosis compared with 9.6% for patients with bacteremia
alone (P = 0.001) and 3.4% for patients with CSF pleocytosis
(P < 0.001) . CNS infection without CSF pleocytosis was
independently associated with adverse outcome by
multivariable logistic regression analysis (P = 0.003) .
CONCLUSIONS: Approximately 30% of all children with IMD
present without CSF pleocytosis . Of these patients those
with CNS infection without pleocytosis are at higher risk of
adverse outcome than either patients with CSF pleocytosis or
patients with bacteremia alone.
Clin Infect Dis, 1998 Oct, 27(4), 746 - 50
Association of human Fc gamma RIIa (CD32) polymorphism with
susceptibility to and severity of meningococcal disease;
Platonov AE et al.; Phagocytosis of bacteria constitutes an
important defense mechanism against invasive bacterial
diseases . Efficacy of phagocytosis by polymorphonuclear
neutrophils is known to vary between allotypes of Fc gamma
RIIa (a class of Fc receptors for immunoglobulins that is
constitutively expressed on neutrophils) . We compared the
distribution of Fc gamma RIIa-R131 and Fc gamma RIIa-H131
allotypes in 98 Slavic complement-sufficient patients with
meningococcal disease with that of the allotypes in 107
healthy controls . A strong association was found between
the IIa-R/R131 allotype and the development of meningococcal
disease after the age of 5 years, compared with IIa-R/H131
and IIa-H/H131 allotypes (P < .03; odds ratio {OR}, 2.9) . A
severe course of meningococcal disease was observed in 21
(68%) of 31 episodes in patients with IIa-R/R131 genotype
and in 22 (54%) of 41 episodes in patients with IIa-R/H131
genotype, in contrast to eight (31%) of 26 episodes in
patients with IIa-H/H131 genotype (P < .02; OR, 4.7) . Our
data show that individuals older than 5 years of age who
have the IIa-H/H131 allotype are less susceptible to severe
meningococcal disease than are individuals with the
IIa-R/R131 or IIa-R/H131 genotype.
Ann Emerg Med, 1998 Nov, 32(5), 620 - 3
Meningococcal meningitis presenting as stroke in an afebrile
adult; Hsu SS et al.; We describe a healthy, afebrile
26-year-old man who presented to the emergency department
with left hemiparesis and cranial nerve deficits caused by
meningococcal meningitis . The results of the computed
tomographic scan of the head were negative . Magnetic
resonance imaging showed lesions in the basal ganglia and
caudate consistent with ischemic infarcts . The neurologic
deficits initially progressed but improved to
near-resolution after 1 month . This case was unusual in
that the patient was afebrile despite a high bacterial load
and significant neurologic deficits . His presentation thus
mimicked a straightforward stroke . Close attention to the
physical examination findings led to a comprehensive
evaluation that yielded the correct diagnosis.
Mol Gen Genet, 1998 Sep, 259(4), 363 - 71
Identification of a hotspot for transformation of Neisseria
meningitidis by shuttle mutagenesis using signature-tagged
transposons; Claus H et al.; Shuttle mutagenesis using
signature-tagged transposons was employed to generate a
library of individually tagged mutants of the Neisseria
meningitidis strain B1940, which belongs to serogroup B .
The use of tagged transposons allowed us to monitor for
enrichment for single mutants during the process of shuttle
mutagenesis, by amplification of the tags and subsequent
sequence determination . Enrichment of a single clone
occurred during the transformation of the meningococci with
transposon-containing plasmid DNA . Sequence determination
around the site of transposon insertion revealed that the
transposon had mutagenized a previously unknown locus, which
was designated hrtA (high rate of transformation) .
hrtA-mediated transformation was independent of TnMax5 and
tag sequences, and it most probably involved recombination
events . The hrtA locus is restricted to meningococci and
gonococci and is present in few apathogenic neisserial
species . Chromosomal mapping of hrtA and six further hrt
sites revealed a random distribution of highly transforming
DNA fragments on the meningococcal chromosome . In
conclusion, our data demonstrate that shuttle mutagenesis of
naturally competent bacteria using signature-tagged
transposons allows the isolation of chromosomal DNA
fragments, which exhibit a high transformation efficiency,
and which, therefore, are likely to be involved in
horizontal gene transfer.
Scand J Infect Dis, 1998, 30(3), 263 - 4
Meningococcal polysaccharide vaccination of military
recruits in Israel: preliminary assessment of vaccine
effect; Mimouni D et al.; Meningococcal disease in the
Israel Defense Force is caused mainly by serogroups C and Y
. Immunization of recruits with quadrivalent polysaccharide
vaccine was introduced in November 1994 . The person-time
incidence rate dropped from 1.33 cases per 100,000
person-years for the preceding decade to 0 for the 32 months
following immunization (p = 0.025).
Cent Eur J Public Health, 1998 Aug, 6(3), 219 - 24
Active surveillance of meningococcal meningitis in Poland;
Tyski S et al.; Starting from 1970, the notification of N .
meningitidis cases in Poland was compulsory and separated
from other cases of meningitis purulenta . Based on the
experience of European Monitoring Group on Meningococci, the
active surveillance of meningococcal meningitis in Poland
was initiated in April 1995 . It was the first time that
such study was conducted to recognise the actual situation
of meningococcal meningitis infections in our country .
Ninety seven N . meningitidis strains were isolated (31 in
1995 and 66 in 1996) from cerebrospinal fluid (CSF) of
meningitis patients hospitalized in 54 hospitals located in
33 out of 49 provinces of Poland . Most patients were below
2 years of age and 43% belonged to infant group .
Meningococcal strains were phenotypically characterized as
follow: identification of N . meningitidis was performed by
Gram staining, oxidase and catalase tests as well as latex
or diagnostic sera agglutination assays . Meningococcal
serotypes and subtypes were determined by whole-cell ELISA
with monoclonal antibodies . The predominant meningococcal
serogroup during 1995 and 1996 was B (80% of all isolates
tested), the serogroup C (12.6%) and W-135 (3.5%) . Only two
non-groupable and two serogroup A strains were isolated in
Poland . Active surveillance allowed to determine B:22:P1.14
to be the most prevalent N . meningitidis phenotype in
Poland . Two isolates of N . meningitidis phenotype
C:2a:P1.2,5, which caused emergency situation in Czech
Republic since 1993, were isolated from CSF of patients in
October 1996 in southern Poland . All strains were
susceptible to cefotaxime, chloramphenicol, ciprofloxacin,
rifampin and tetracycline; some strains were resistant to
sulphonamides (60.6% - MIC = 32 mg/l and 14.8% - MIC = 128
mg/l) . Only one of the tested strains in two years
surveillance study in Poland was resistant to penicillin
(MIC = 2 mg/l).
J Antimicrob Chemother, 1998 Sep, 42(3), 303 - 7
The detection of penicillin insensitivity in Neisseria
meningitidis by polymerase chain reaction; Maggs AF et al.;
Strains of penicillin-sensitive and -insensitive Neisseria
meningitidis were examined using a range of polymerase chain
reaction (PCR) primers directed at the meningococcal
penicillin-binding protein 2 gene . DNA from isolates whose
penicillin MIC was <0.2 mg/L yielded a product of the
expected size with all the primers, but many amplification
patterns were seen with DNA from isolates whose MIC was
above this level . All strains whose MIC was >0.25 mg/L
failed to produce a product of the expected size with at
least one of the primers used . The changes seen in
penicillin-insensitive strains were consistent with
horizontal gene transfer from Neisseria flavescens in some
isolates, although the source for others remains unknown .
PCR-based methods for the detection of antibiotic resistance
are becoming increasingly important with the expanding use
of molecular techniques for bacteriological diagnosis.
J Accid Emerg Med, 1998 Sep, 15(5), 298 - 303
Avoidable deficiencies in the delivery of health care to
children with meningococcal disease; Nadel S et al.;
OBJECTIVES: It is apparent that delays and inadequate or
inappropriate management occur frequently and may contribute
to the continued high mortality seen in meningococcal
disease . An attempt has been made to define the major
sources of delay or inappropriate treatment . METHODS: A
prospective, descriptive study of children with
meningococcal disease referred to a tertiary centre
paediatric intensive care and infectious disease unit .
Definitions of optimal care were established at three
stages: parental; general practitioner (GP)/accident and
emergency (A&E) department; and hospital . Duration of
symptoms and management were recorded from direct
questioning of parents and carers, and from hospital records
. RESULTS: 54 consecutive children with meningococcal
disease were recruited to the study . Delayed parental
recognition occurred in 16 children . GPs correctly
diagnosed 19 of 35 children . Delay of 2.5-21 hours occurred
in those who were incorrectly diagnosed . Two of 15 children
who presented to the A&E department with specific features
were incorrectly diagnosed . Hospital treatment was
suboptimal in 71% . Shock was not recognised or treated in
50%, 20% of children had unnecessary lumbar punctures . Time
from illness onset to treatment was longer in fatal disease
(median 18.3, range 8-24 hours), compared with survivors
(median 12, range 2-48 hours; p < 0.01, Mann-Whitney U test)
. CONCLUSION: Suboptimal treatment in meningococcal disease
is due to failure of parents, GPs, and hospital doctors to
recognise specific features of the illness . Improvement by
public education and better training of clinicians in
recognition, resuscitation, and stabilisation of seriously
ill children.
Infect Immun, 1998 Nov, 66(11), 5350 - 6
Complement activation in relation to capillary leakage in
children with septic shock and purpura; Hazelzet JA et al.;
To assess the relationship between capillary leakage and
inflammatory mediators during sepsis, blood samples were
taken on hospital admission, as well as 24 and 72 h later,
from 52 children (median age, 3.3 years) with severe
meningococcal sepsis, of whom 38 survived and 14 died .
Parameters related to cytokines (interleukin 6 {IL-6} IL-8,
plasma phospholipase A2, and C-reactive protein {CRP}), to
neutrophil degranulation (elastase and lactoferrin), to
complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP
complexes), and to complement regulation (functional and
inactivated C1 inhibitor and C4BP) were determined . The
degree of capillary leakage was derived from the amount of
plasma infused and the severity of disease by assessing the
pediatric risk of mortality (PRISM) score . Levels of IL-6,
IL-8, C3b/c, C3-CRP complexes, and C4BP on admission,
adjusted for the duration of skin lesions, were
significantly different in survivors and nonsurvivors (C3b/c
levels were on average 2.2 times higher in nonsurvivors, and
C3-CRP levels were 1.9 times higher in survivors) .
Mortality was independently related to the levels of C3b/c
and C3-CRP complexes . In agreement with this, levels of
complement activation products correlated well with the
PRISM score or capillary leakage . Thus, these data show
that complement activation in patients with severe
meningococcal sepsis is associated with a poor outcome and a
more severe disease course . Further studies should reveal
whether complement activation may be a target for
therapeutical intervention in this disease.
Pediatr Infect Dis J, 1998 Sep, 17(9), 816 - 9
Azithromycin compared with rifampin for eradication of
nasopharyngeal colonization by Neisseria meningitidis;
Girgis N et al.; OBJECTIVES: To evaluate the efficacy and
safety of azithromycin compared with rifampin for
eradication of nasopharyngeal carriage of Neisseria
meningitidis METHODS: Pharyngeal swabs were obtained from
500 students attending nursing school in Cairo, Egypt, to
determine the colonization rate with N . meningitidis .
Colonized individuals were randomized to receive
azithromycin (500 mg once) or rifampin (600 mg twice daily
for four doses) . Subjects were then recultured 1 and 2
weeks posttreatment to determine the effectiveness of the
antibiotic therapy for eradication of meningococcal
nasopharyngeal colonization . RESULTS: Individuals treated
with azithromycin had a 93% eradication rate at 1 and 2
weeks posttreatment comparable with 95 and 91%,
respectively, for rifampin . No significant side effects
were reported by any subjects treated with either antibiotic
. CONCLUSION: Azithromycin is effective in the eradication
of N . meningitidis from the nasopharynx of asymptomatic
colonized individuals and deserves further evaluation for
use as prophylaxis against N . meningitidis.
MMWR Morb Mortal Wkly Rep, 1998 Oct 9, 47(39), 833 - 7
Outbreaks of group B meningococcal disease--Florida, 1995
and 1997; Matrix metalloproteinases contribute to the
blood-brain barrier disruption during bacterial meningitis;
Department of Neurology, Ludwig-Maximilians-University of
Munich, Klinikum Brosshadern, GermanyIn this study, we
investigated the involvement of matrix metalloproteinases
(MMPs) in the pathophysiology of bacterial meningitis . By
using an enzyme immunoassay, high concentrations of MMP-9
were detected in the cerebrospinal fluid (CSF) of adult
patients with bacterial meningitis but not in controls, and
in patients with Guillain-Barre syndrome . Moreover, we
observed significantly elevated concentrations of the tissue
inhibitor of metalloproteinase-1 (TIMP-1) in the CSF of
patients with bacterial meningitis, compared with controls .
In a rat model of meningococcal meningitis, intracisternal
injection of heat-killed meningococci caused a disruption of
the blood-brain barrier (BBB), an increase in intracranial
pressure, and CSF pleocytosis paralleled by the occurrence
of MMP-9 activity in the CSF 6 hours after meningococcal
challenge . The MMP inhibitor batimastat (BB-94)
significantly reduced the BBB disruption and the increase in
intracranial pressure irrespective of the time of batimastat
administration (15 minutes before and 3 hours after
meningococcal challenge) but failed to significantly reduce
CSF white blood cell counts . In conclusion, our results
suggest that MMPs are involved in the alterations of BBB
permeability during experimental meningococcal meningitis.
Rev Cubana Med Trop, 1996, 48(1), 34 - 9
{Meningococcal disease and VA-MENGOC BC in minors less than
1 year of age . Cuba, 1983 to 1991}; Rico Cordeiro O et al.;
A study of the chronological series of mortality due to
meningococcal disease in children under one year old, the
group of highest incidence during the last epidemy in Cuba,
was carried out . Data were collected by doing a survey in
an uniform way since 1983 throughout the country . More than
90% of the population between 3 months and 5 years old were
vaccinated with VAMENGOC BC since the end of 1988 until
April, 1990 . The behaviour of this disease was studied in
order to identify the influence of this vaccine . It is
stressed that the mortality incidence reached its epidemic
achme in 1986 and begins a slow descence which is
accentuated in 1990 and 1991, with an annual relative
decrease of 26.1 and 34.9%, respectively . The highest
mortality rate was found in 1984, with a significant
reduction in 1990 (-23.8%) and 1991 (-41.8%), after the
culmination of the vaccination campaign with VA-MENGOC BC .
It was detected that morbimortality, which is lower in
children under one month because of the probable protection
provided by maternal antibodies, started to increase until
the fifth month of life, when it is observed a trend towards
the reduction of morbidity and mortality . According to the
present immunization chronogram, overall protection in only
attained after the sixth mont of life.
Mol Microbiol, 1998 Aug, 29(4), 975 - 84
Identification of a novel gene involved in pilin
glycosylation in Neisseria meningitidis; Jennings MP et al.;
The pili of Neisseria meningitidis are a key virulence
factor, being major adhesins of this capsulate organism that
contribute to specificity for the human host . Recently it
has been reported that meningococcal pili are
post-translationally modified by the addition of an O-linked
trisaccharide, Gal (beta1-4) Gal (alpha1-3)
2,4-diacetimido-2,4,6-trideoxyhexose . Using a set of random
genomic sequences from N . meningitidis strain MC58, we have
identified a novel gene homologous to a family of
glycosyltransferases . A plasmid clone containing the gene
was isolated from a genomic library of N . meningitidis
strain MC58 and its nucleotide sequence determined . The
clone contained a complete copy of the gene, here designated
pglA (pilin glycosylation) . Insertional mutations were
constructed in pglA in a range of meningococcal strains with
well-defined lipopolysaccharide (LPS) or pilin-linked glycan
structures to determine whether pglA had a role in the
biosynthesis of these molecules . There was no alteration in
the phenotype of LPS from pglA mutant strains as judged by
gel migration and the binding of monoclonal antibodies . In
contrast, decreased gel migration of the pilin subunit
molecules of pglA mutants was observed, which was similar to
the migration of pilins of galE mutants of same strains,
supporting the notion that pglA is a glycosyltransferase
involved in the biosynthesis of the pilin-linked
trisaccharide structure . The pglA mutation, like the galE
mutation reported previously, had no effect on
pilus-mediated adhesion to human epithelial or endothelial
cells . Pilin from pglA mutants were unable to bind to
monospecific antisera recognizing the Gal (beta1-4) Gal
structure, suggesting that PglA is a glycosyltransferase
involved in the addition of galactose of the trisaccharide
substituent of pilin.
Res Microbiol, 1998 Jun, 149(6), 381 - 7
Cooperation between the components of the meningococcal
transferrin receptor, TbpA and TbpB, in the uptake of
transferrin iron by the 37-kDa ferric-binding protein
(FbpA); Gomez JA et al.; Meningococcal TbpAB complexes TbpA,
TbpB and FbpA were purified and used to study their role in
the uptake of iron from transferrin to FbpA . Purification
was achieved by affinity chromatography techniques, yielding
homogeneous, non-denatured and functional material . TbpA
could not be separated from TbpB and had to be purified from
a TbpB-defective mutant strain . FbpA was able to bind iron
from transferrin only when TbpAB complexes, TbpA and/or
TbpB, were also present during the interaction . The highest
uptake efficiences were obtained with TbpAB complexes or
TbpA/TbpB mixtures . We conclude that the TbpA and TbpB
molecules form true functional transferrin receptors, that
FbpA is able to take iron directly from transferrin when in
the presence of the components of the receptor, and that
both Tbps are necessary for an optimal operation of the
uptake system.
Acta Crystallogr D Biol Crystallogr, 1998 Sep 1, 54 ( Pt 5),
1005 - 7
Crystallization and preliminary X-ray diffraction analysis
of antigen-binding fragments which are specific for
antigenic conformations of sialic acid homopolymers;
Patenaude SI et al.; Meningococcal meningitis is a severe
childhood disease which often results in significant
disability or death . Two major etiological agents of
meningitis are the group B meningococci and capsular type K1
E . coli . The virulence of these organisms is attributable
to structural mimicry between their common
alpha(2-8)-polysialic acid capsular polysaccharide and human
tissue antigens, which allows the bacteria to evade immune
surveillance . There is currently no effective vaccine to
protect against this infection . It has been demonstrated
that the capsular polysaccharide of the bacteria can adopt a
unique 'antigenic conformation' . This antigenic
conformation has formed the basis for the development of an
N-propionylated polysialic acid vaccine . Immunization
trials in mice with this vaccine show the production of two
groups of antibodies, of which only N-propionylated
polysialic acid-specific were protective . Knowledge of the
structure of the antigen-binding site which recognizes the
protective epitope is essential to determining the antigenic
conformation of the polysaccharides, and is a critical
aspect in understanding and improving the action of
potential vaccines . The antigen-binding fragments (Fab) of
one protective (13D9) and one non-protective (6B9)
monoclonal antibody specific for the capsular
polysaccharides of group B meningococci have been
crystallized and have undergone preliminary X-ray
diffraction analysis . Both crystals are observed to scatter
X-rays to approximately 1.7 A resolution at the A1 station
at the Cornell High-Energy Synchrotron Source . 13D9 has an
orthorhombic unit cell with a = 41.8, b = 102.3, c = 134.7
A, with space group P212121 . Fab 6B9 has an orthorhombic
unit cell with a = 89.6, b = 132.0 and c = 36.9 A, with
space group P21212.
Rev Inst Med Trop Sao Paulo, 1998 Mar-Apr, 40(2), 113 - 7
The use of oligonucleotide probes for meningococcal serotype
characterization; Sacchi CT et al.; In the present study we
examine the potential use of oligonucleotide probes to
characterize Neisseria meningitidis serotypes without the
use of monoclonal antibodies (MAbs) . Antigenic diversity on
PorB protein forms the bases of serotyping method . However,
the current panel of MAbs underestimated, by at least 50%
the PorB variability, presumably because reagents for
several PorB variable regions (VRs) are lacking, or because
a number of VR variants are not recognized by
serotype-defining MAbs . We analyzed the use of
oligonucleotide probes to characterize serotype 10 and
serotype 19 of N . meningitidis . The porB gene sequence for
the prototype strain of serotype 10 was determined, aligned
with 7 other porB sequences from different serotypes, and
analysis of individual VRs were performed . The results of
DNA probes 21U (VR1-A) and 615U (VR3-B) used against 72 N .
meningitidis strains confirm that VR1 type A and VR3 type B
encode epitopes for serotype-defined MAbs 19 and 10,
respectively . The use of probes for characterizing
serotypes possible can type 100% of the PorB VR diversity .
It is a simple and rapid method specially useful for
analysis of large number of samples.
Rev Inst Med Trop Sao Paulo, 1998 Mar-Apr, 40(2), 65 - 70
Meningococcal disease caused by Neisseria meningitidis
serogroup B serotype 4 in São Paulo, Brazil, 1990 to 1996;
Sacchi CT et al.; A large epidemic of serogroup B
meningococcal disease (MD), has been occurring in greater
Sao Paulo, Brazil, since 1988 . A Cuban-produced vaccine,
based on outer-membrane-protein (OMP) from serogroup B:
serotype 4: serosubtype P1.15 (B:4:P1.15) Neisseria
meningitidis, was given to about 2.4 million children aged
from 3 months to 6 years during 1989 and 1990 . The
administration of vaccine had little or no measurable
effects on this outbreak . In order to detect clonal changes
that could explain the continued increase in the incidence
of disease after the vaccination, we serotyped isolates
recovered between 1990 and 1996 from 834 patients with
systemic disease . Strains B:4:P1.15, which was detected in
the area as early as 1977, has been the most prevalent
phenotype since 1988 . These strains are still prevalent in
the area and were responsible for about 68% of 834 serogroup
B cases in the last 7 years . We analyzed 438 (52%) of these
strains by restriction fragment length polymorphism (RFLPs)
of rRNA genes (ribotyping) . The most frequent pattern
obtained was referred to as Rb1 (68%) . We concluded that
the same clone of B:4:P1.15-Rb1 strains was the most
prevalent strain and responsible for the continued increase
of incidence of serogroup B MD cases in greater Sao Paulo
during the last 7 years in spite of the vaccination trial.
Trop Med Int Health, 1998 Sep, 3(9), 742 - 6
Meningitis caused by a serogroup W135 clone of the ET-37
complex of Neisseria meningitidis in West Africa; Kwara A et
al.; Meningococci belonging to serogroup W135 caused several
cases of meningococcal meningitis in The Gambia in 1995 and
were isolated during a serogroup A epidemic in Mali in 1994
. The eight isolates tested belonged to the same clone of
the ET-37 complex and differed in several bands from the
pulsed-field gel electrophoresis restriction pattern of
serogroup C meningococci of the ET-37 complex isolated in
Mali . Three of 6 patients infected in The Gambia died,
indicating that this W135 clone is virulent . Vaccines that
protect only against infections with meningococci belonging
to serogroups A and C are usually used to control outbreaks
in Africa, although vaccines containing the W135
polysaccharide are available . The findings of this study
indicate that outbreaks of meningococcal meningitis in
Africa can be associated with serogroup W135 infections and
that serogrouping is essential before vaccination campaigns
are started.
Epidemiol Infect, 1998 Aug, 121(1), 95 - 101
Molecular variation of meningococcal serotype 4 antigen
genes; Urwin R et al.; Changes in the frequency of serogroup
B non serotypable (B:NT) meningococci isolated in England
and Wales were investigated by T-track fingerprint analysis,
DNA nucleotide sequence determination, and serotyping by
whole cell ELISA and dot blot assay . Seventy-three per cent
of the isolates designated as B:NT by the Meningococcal
Reference Unit (MRU) dot blot assay during 1993-4, expressed
variants of the serotyping antigen, PorB, that were serotype
4 by whole cell ELISA . T-track fingerprint patterns of
these and other 'serotype 4' isolates revealed five distinct
porB alleles which were shown by nucleotide sequence
determination to encode different peptide sequences .
Differential binding of the 'serotype 4' mAbs MN14G21 and
5DC4C8G8 in whole cell ELISA and dot blot assays was the
result, (i) of differences in the peptide sequence of
predicted surface loop I and (ii) an amino acid deletion in
predicted loop VI of the PorB protein.
Epidemiol Infect, 1998 Aug, 121(1), 85 - 94
Dynamics of the meningococcal carrier state and
characteristics of the carrier strains: a longitudinal study
within three cohorts of military recruits; Andersen J et
al.; Three cohorts of Danish male military recruits (n =
1069) were studied for pharyngeal meningococcal carriage
during 3 months at different seasons: 39-47% of entrants
were meningococcal carriers and the carriage rate remained
constant over time and season . However, individual changes
in the carrier state occurred frequently, and after 3 months
34% had changed carrier state on one or more occasions .
Initially, a loss of carriage predominated; on the other
hand almost 20% of non-carriers had acquisition of
meningococci within the first month . The serological
phenotypes of the 670 carrier strains were compared with
those of 261 invasive strains recovered concurrently from
patients with meningococcal disease country-wide . Both
carrier strains and invasive strains were phenotypically
heterogeneous . Almost 60% of the invasive strains belonged
to three phenotypes: B:15:P1.7, 16, C:2a:P1.2, 5 and
C:2b:P1.2, 5 . In contrast, these phenotypes only amounted
to 3.2% of the carrier strains, among which no phenotype was
found with a prevalence above 4.9% . However, 30% of the
carrier strains had serological phenotypes identical to
those of 80% of the invasive strains . Our results indicated
that the transmission rate of potential pathogenic carrier
strains did not differ from that of other carrier strains.
Infect Immun, 1998 Oct, 66(10), 4755 - 61
Specificity of bactericidal antibody response to serogroup B
meningococcal strains in Brazilian children after
immunization with an outer membrane vaccine; Milagres LG et
al.; Pre- and postvaccination serum samples from 77 children
aged 2 to 6 years, who received the Cuban BC vaccine
(B:4:P1.15), were analyzed for bactericidal antibodies
against a local B:4:P1.15 strain (N44/89) . Sera from 16
individuals with bactericidal antibodies against the
B:4:P1.15 strain were tested against 23 Brazilian isolates .
These include B:4 strains of distinct serosubtypes: P1.15,
P1.7,1, P1.3, P1.9, P1.nt, and a B:8,19,23:P1.16 strain . A
Cuban B:4:P1.15 strain (Cu385/83) was also included in the
study . The specificities of bactericidal antibodies were
analyzed by using mutant strains lacking a class 1 protein
(PorA protein) or a class 5 protein or both . The results
indicated that PorA and class 5 proteins are the main
targets recognized by the bactericidal antibodies of
vaccinees . Nonetheless, a complex pattern of recognition by
bactericidal antibodies was found, and vaccinees were
grouped according to antibody specificity . Antibodies from
some individuals recognized PorA of serosubtype P1.15 .
However, antibodies from these individuals could not kill
all P1.15 strains tested . Antibodies from a second group
recognized both PorA and class 5 proteins, and antibodies
from a third group recognized an as yet unidentified target
antigen . The results demonstrate the importance of
determining the fine epitope specificity of bactericidal
antibodies to improve the existing vaccines against B
meningococci.
J Clin Microbiol, 1998 Oct, 36(10), 3103 - 4
Unreliability of disc diffusion test for screening for
reduced penicillin susceptibility in Neisseria meningitidis;
Block C et al.; The 2-U penicillin and microgram oxacillin
discs proposed for screening meningococci for susceptibility
to penicillin were evaluated by using MICs measured by the E
test . The discs yielded unacceptably high frequencies of
misclassification of susceptibility category and should be
abandoned in favor of MIC estimations . An agreed breakpoint
for reduced penicillin susceptibility in meningococci is
needed for the E test.
J Clin Microbiol, 1998 Oct, 36(10), 2828 - 34
Molecular epidemiology of recent belgian isolates of
Neisseria meningitidis serogroup B; Van Looveren M et al.;
In Belgium an increase in the incidence of meningococcal
disease has been noted since the early 1990s . Four hundred
twenty clinical strains isolated during the period from 1990
to 1995, along with a set of 30 European reference strains,
and 20 Dutch isolates were examined by random-primer and
repetitive-motif-based PCR . A subset was investigated by
multilocus enzyme electrophoresis and pulsed-field gel
electrophoresis . The data were compared with results
obtained by serotyping (M . Van Looveren, F . Carion, P .
Vandamme, and H . Goossens, Clin . Microbiol . Infect .
4:224-228, 1998) . Both phenotypic and molecular
epidemiological data suggest that the lineage III of
Neisseria meningitidis, first encountered in The Netherlands
in about 1980, has been introduced in Belgium . The epidemic
clone, as defined by oligonucleotide D8635-primed PCR,
encompasses mainly phenotypes B:4:P1.4 and
B:nontypeable:P1.4, but strains with several other
phenotypes were also encountered . Therefore, serotyping
alone would underestimate the prevalence of the epidemic
clone.
J Biol Chem, 1998 Sep 25, 273(39), 25329 - 38
Characterization of the structure, function, and
conformational stability of PorB class 3 protein from
Neisseria meningitidis . A porin with unusual
physicochemical properties; Minetti CA et al.; PorB proteins
constitute the vast majority of channels in neisserial outer
membranes and can be subdivided within meningococcal strains
into two distinct and mutually exclusive families that are
designated as class 2 and class 3 proteins . We recently
characterized the functional activity and conformational
stability of a PorB class 2 protein from Neisseria
meningitidis (Minetti, C . A . S . A., Tai, J . Y., Blake, M
. S., Pullen, J . K., Liang, S . M., and Remeta, D . P .
(1997) J . Biol . Chem . 272, 10710-10720) . To evaluate the
structure-function relatedness among the PorB proteins, we
have employed a combination of electrophoretic and
spectroscopic techniques to assess the conformational
stability of zwittergent-solubilized class 3 trimers . The
functional, physicochemical, and structural properties of
the meningococcal class 2 and class 3 proteins are
comparable with the notable exception that the latter
exhibits a significantly higher susceptibility to SDS . The
SDS-induced dissociation and partial unfolding of PorB class
3 is characterized by a single two-state transition with a
midpoint at 0.35% SDS . The native trimeric assembly
dissociates reversibly, forming partially folded monomers
that retain the characteristic beta-sheet content of the
transmembrane domain with a concomitant increase in random
coil structure arising from unfolding the rigid surface
loops . These results provide new insight into the
elucidation of porin folding pathways and the factors that
govern the overall structural stability of meningococcal
proteins.
J Med Microbiol, 1998 Sep, 47(9), 757 - 60
Analysis of TbpA and TbpB functionality in defective mutants
of Neisseria meningitidis; Pintor M et al.; Iron uptake
analysis suggested that the Neisseria meningitidis
transferrin (Tf) binding proteins, TbpA and TbpB, form only
one type of receptor complex . Mutants defective in the
synthesis of either TbpA or TbpB, but not defective in both
proteins, can bind Tf, suggesting that both proteins are
surface exposed and function in Tf binding . Also, iron
uptake from Tf into the meningococci did not require the
presence of both Tbps . The TbpB-defective mutant
incorporated c . 37% of the iron taken up by the wild-type
strain, but this was insufficient for bacterial growth . The
TbpA-defective mutant incorporated c . 50% of the iron taken
up by the wild-type strain and was able to grow with Tf as
the only iron source . Mouse antibodies specific for TbpA
were able to block c . 70% of the iron uptake from Tf in the
wild-type strain, whereas they blocked only 22% of iron
uptake in the TbpB-defective mutant and did not block uptake
in the TbpA-defective strain . These results emphasise that
TbpA should be considered in future vaccine trials in which
iron-restricted proteins are to be included in the vaccine
formulation.
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