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MENINGITE e VACCINI - Bibliografia
(English) - Pag. 5
(nome scientifico = encefalite post-vaccinica)

Continua in: Pag. 1 - Pag. 2 -  Pag. 3 - Pag. 4 + 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
- Encefalite post Vaccinica - creata e prodotta dai VACCINI

Associazione temporale di alcuni disturbi NeuroPsichiatrici DOPO la vaccinazione di bambini e adolescenti:
Uno studio Pilota con  casi-controllo

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

L’INCUBO "MENINGITE", il presunto nuovo TEST che invece “CREA” e diffonde, assieme ai VACCINI Pediatrici, l’EPIDEMIA.

Fino a ieri i DISINFORMATORI degli enti a tutela della salute, si ma di quella dei fatturati di Big Pharma, dicevano che i vaccini "proteggono dalle malattie", guardate invece cosa succede:

Med Sci Law
, 1998 Jan, 38(1), 52 - 6
Digoxin-like immunoreactivity in early infantile death; Couper RT et al.; The aim of this study was to determine if the level of digoxin-like immunoreactivity in post-mortem sera obtained from infants differs according to the cause of death and if the level is related to age, post-mortem interval, cardiac pathology or adrenal weight . Twelve infants whose deaths were attributed to sudden infant death syndrome (SIDS), and 11 infants who died from other causes, had blood sampled between 3 to 53 hours post-mortem from their right atrial cavity . Digoxin-like immunoreactivity was measured, using a specific and sensitive digoxin radioimmunoassay, and was detected in 7 of the infants who died of SIDS and 7 of those who died from other causes . The highest levels were seen in two patients who died from meningococcal sepsis and haemorrhage, hyperpyrexia and encephalopathy syndrome, respectively .
No correlation was detected between the digoxin-like immunoreactivity level, gender, age at death, post-mortem interval or cardiac pathology . Digoxin-like immunoreactivity levels correlated with adrenal weight . It is concluded that digoxin-like immunoreactivity is frequently found in infant sera, but levels are not specific to and are no higher in SIDS infants than infants dying of other conditions.

Immunol Res, 1998, 17(1-2), 95 - 108
Peptide mimotopes of carbohydrate antigens; Kieber-Emmons T; Carbohydrate structures have been identified as significant antigens for bacterial, viral, and fungal pathogens as well as targets on human tumor cells . Many of these antigens are poorly immunogenic in humans, requiring extensive adjuvant sublimation . Although conjugate carbohydrate vaccines appear promising, there are limitations of using carbohydrate formulations . An alternative approach is to use surrogate antigens for some carbohydrates . We are developing peptides that mimic carbohydrates which might be further manipulated to induce responses that target biologically important carbohydrates expressed on pathogens and on tumor cells . We have shown that peptide mimotopes of carbohydrates induce immune responses to carbohydrate structures with in vivo and vitro functionality . Model systems include the Neisseria group C meningococcal polysaccharide; the histo-blood group-related antigens expressed on tumor cells; and mannose, sialyl, and histo-blood group-related carbohydrate epitopes expressed on human immunodeficiency virus.

World Health Stat Q, 1997, 50(3-4), 170 - 7
Meningococcal disease: public health burden and control; Tikhomirov E et al.; Meningococcal disease which is increasing globally is still associated with a high mortality and persistent neurological defects, particularly among infants and young children . Sporadic meningococcal meningitis occurs throughout the world, with seasonal variations, and accounts for 10-40% of endemic bacterial meningitis . Epidemic meningitis occurs in any part of the world but the largest and most frequently recurring epidemics have been in the semi-arid area of sub-Saharan Africa where the current pandemic is associated with attack rates exceeding 500 per 100,000 population and thousands of deaths . In the Americas and Europe serogroup B is the predominant agent causing systemic disease, followed in frequency by serogroup C . Serogroup A meningococcus was historically the main cause of epidemic meningococcal disease globally and still predominates in Africa and Asia . A range of internal and external factors predispose for epidemics such as strain virulence, carriers, humoral immunity, co-infections, low humidity and drought, population movements and crowding . To respond to the current situation and the expected spread of the disease, WHO, in collaboration with its Member States and various governmental and non-governmental agencies, has developed a sustainable plan of action for preparedness and control of meningitis.

Int J Cardiol, 1997 Dec 19, 62(3), 277 - 8
Asymptomatic temporary atrioventricular dissociation complicating meningococcal meningitis; Shapira MY et al.; We present a case of a young man with meningococcal meningitis and various asymptomatic temporary ECG abnormalities, including sinus bradycardia, atrioventricular dissociation and non specific ST-T changes.

Immunopharmacology, 1997 Dec, 38(1-2), 93 - 9
The effect of mannan-binding lectin on opsonophagocytosis of Neisseria meningitidis; Drogari-Apiranthitou M et al.; Mannan-binding lectin (MBL), an acute phase protein with a structure and a function very similar to that of C1q, is known to act as an opsonin binding to a number of microorganisms . In order to investigate the effect of MBL on the phagocytic killing of meningococci, a serogroup B meningococcal strain (H44/76) and its unencapsulated variant v24, as well as a serogroup A meningococcal strain were opsonized with MBL (purified from normal human plasma at the State Serum Institute, Denmark) and used in a phagocytic killing assay at a density of 7 x 10(3) CFU/ml . Polymorphonuclear cells (PMNs) from one healthy donor were isolated by density gradient centrifugation over Percoll and added to the system (7 x 10(6) cells/ml) . In a first set of experiments without addition of serum or complement, no influence of MBL was observed on the killing of any of these strains . Addition of MBL to non-opsonized bacteria of the serogroup A strain did not result in enhanced killing either; on the contrary, the growth of this strain increased significantly when a high MBL concentration (40 micrograms/ml) was used in the presence of PMNs . Further investigations were performed using sera of five individuals with late complement component deficiency (LCCD) and a concomitant MBL deficiency, vaccinated with a tetra-valent (ACYW135) meningococcal capsular polysaccharide vaccine . Pre- and post-vaccination sera (50% final concentration) were tested against a group A strain opsonized or not with MBL . In only one patient was there a moderate increase of killing of the opsonized bacteria after vaccination compared to pre-vaccination serum. Our results suggest that MBL may not play a significant role in the opsonophagocytosis of meningococci, irrespective of its binding to unencapsulated and serogroup A strains.

Clin Exp Immunol, 1998 Jan, 111(1), 97 - 101
Meningococcal disease and polymorphism of FcgammaRIIa (CD32) in late complement component-deficient individuals; Platonov AE et al.; Late complement component-deficient (LCCD) individuals lack plasma bactericidal activity and are highly susceptible to meningococcal disease . Phagocytosis plays a significant role in immune defence against meningococci and involves FcgammaRIIa (CD32) on leucocytes . Two allotypic forms are currently recognized: FcgammaRIIa-R131 and RIIa-H131 . Neutrophils with the IIa-H/H131 allotype are more effective in phagocytosis than IIa-R/R131 . We studied the distributions of IIa-R131 and IIa-H131 allotypes among 29 Russian LCCD patients who had suffered from recurrent episodes of meningococcal disease . The distribution of IIa-R/R131 to heterozygous IIa-R/H131 to homozygous IIa-H/H131 genotypes was 0.14:0.29:0.57 for LCCD patients who developed the first episode of disease before 10 years of age . The distribution was 0.21:0.64:0.14 for patients who experienced meningococcal disease above the age of 10 years (chi2 = 6, P < 0.05, odds ratio for IIa H/H131 versus R/R131 = 8) . Meningococcal disease had a 'grave' course in 14 of 31 disease episodes in patients with IIa-R/R131 and IIa-R/H131 allotypes, in contrast to 1 of 18 episodes in patients with IIa-H/H131 allotype (chi2 = 7, P < 0.01, odds ratio = 14) . We conclude that IIa-H/H131 individuals appear to have a higher acquired antibody-mediated phagocytosis-dependent resistance to meningococcal disease above the age of 10 years . Additionally, effective CD32-mediated phagocytosis may restrict the severity of meningococcal disease in LCCD patients with IIa-H/H131 phenotype.

Clin Exp Immunol, 1998 Jan, 111(1), 91 - 6
Molecular defects leading to human complement component C6 deficiency in an African-American family; Zhu ZB et al.; Complement component C6 deficiency (C6D) was diagnosed in a 16-year-old African-American male with meningococcal meningitis . The patient's father and two brothers also had C6D, but gave no history of meningitis or other neisserial infection . By using exon-specific polymerase chain reaction (PCR)/single-strand conformation polymorphism as a screening step and nucleotide sequencing of target exons, we determined that the proband was a compound heterozygote for two C6 gene mutations . The first, 1195delC located in exon 7, is a novel mutation, while the second, 1936delG in exon 12, has been described before to cause C6D in an unrelated African-American individual . Both mutations result in premature termination codons and C6 null alleles . Allele-specific PCR indicated that the proband's two brothers also inherited the 1195delC mutation from their heterozygous mother and the 1936delG mutation from their homozygous father.

BMJ, 1998 Jan 24, 316(7127), 276 - 9
Recognising meningococcal disease in primary care: qualitative study of how general practitioners process clinical and contextual information; Granier S et al.; OBJECTIVES: To describe the presentation of meningococcal disease in primary care; to explore how general practitioners process clinical and contextual information in children with meningococcal disease; and to describe how this information affects management . DESIGN: Qualitative analysis of semistructured interviews . SETTING: General practices in South Glamorgan . SUBJECTS: 26 general practitioners who between January 1994 and December 1996 admitted 31 children (under 16 years of age) in whom meningococcal disease was diagnosed . MAIN OUTCOME MEASURES: Categories of clinical rules and techniques used by general practitioners in processing each case . RESULTS: 22 children had rashes; in 16 of them the rashes were non-blanching . When present, a haemorrhagic rash was the most important factor in the doctor's decision to admit a child . 22 children had clinical features not normally expected in children with acute self limiting illnesses--for example, lethargy, poor eye contact, altered mental states, pallor with a high temperature, and an abnormal cry . Contextual information, such as knowledge of parents' consultation patterns and their normal degree of anxiety, played an important part in the management decisions in 15 cases . Use of penicillin was associated with the certainty of diagnosis and the presence and type of haemorrhagic rash . CONCLUSION: The key clinical feature of meningococcal disease--a haemorrhagic rash--was present in only half of the study children . The general practitioners specifically hunted for the rash in some ill children, but doctors should not be deterred from diagnosing meningococcal disease and starting antibiotic treatment if the child is otherwise well, if the rash has an unusual or scanty distribution, or if the rash is non-haemorrhagic.

Epidemiol Mikrobiol Imunol, 1997 Dec, 46(4), 145 - 8
{Changes in clinical and epidemiologic characteristics in Western Bohemia of invasive meningococcal disease associated with the occurrence of an invasive clone of Neisseria meningitidis}; Struncova V et al.; The authors analyzed the incidence of meningococcal diseases in the West Bohemian region in 1982-1996 . The draw attention to changes of clinical and epidemiological characteristics of the disease which appeared in 1994 in conjunction with a new invasive clonus of Neisseria meningitidis C:2a:P1.2, P1.5, ET-15/37 . While in 1982-1993 invasive meningococcal diseases had in 75% the course of meningitis with a relatively low fatality (4%), during the subsequent period a marked change occurred . Since 1994 the disease took in the West Bohemian region in 58% the course of sepsis with a fatality of 16% . 25% cases of meningococcal meningitis were diagnosed combined sepsis and meningitis in 17% . The disease lost its seasonal character and the authors confirmed the highest incidence of the disease in the age group from 15-19 years and 0-4 years . Neisseria meningitidis group C was detected in 1994-1996 in 73% and the invasive clone C:2a:P1.2, P1.5, ET-15/37 in 62%.

Microbiology, 1998 Jan, 144 ( Pt 1), 157 - 66
Recombinational reassortment among opa genes from ET-37 complex Neisseria meningitidis isolates of diverse geographical origins; Hobbs MM et al.; Opacity (Opa) proteins are a family of antigenically variable outer-membrane proteins of Neisseria meningitidis . ET-37 complex meningococci, defined by multilocus enzyme electrophoresis, have been isolated on different continents . Twenty-six different Opa proteins have been observed within strains of the ET-37 complex isolated between the 1960s and the 1980s, although individual strains have only four opa genes per chromosome . In this work the opa genes of four closely related ET-37 complex N . meningitidis strains recently isolated from Mali, West Africa were characterized and compared with the opa genes of strain FAM18, an ET-37 complex isolate from the USA . DNA sequence analysis and Southern blot experiments indicated that recombinational reassortment, including gene duplication and import by horizontal genetic exchange, has occurred in the opa genes within the ET-37 complex, resulting in two partially different Opa repertoires being present in FAM18 and the Mali isolates . Using synthetic peptides derived from the hypervariable (HV) regions of opa genes, the epitopes for nine mAbs were mapped . These bacteria, isolated on different continents, contain both shared and unique opa HV regions encoding epitopes recognized by mAbs and show evidence of recombinational reassortment of the HV regions.

JAMA, 1998 Feb 11, 279(6), 435 - 9
Efficacy of meningococcal vaccine and barriers to vaccination; Rosenstein N et al.; CONTEXT: Use of the quadrivalent meningococcal vaccine for control of outbreaks has increased in recent years, but the efficacy of meningococcal vaccine during mass vaccination campaigns in US civilian populations has not been assessed . OBJECTIVES: To evaluate the efficacy of the quadrivalent meningococcal vaccine against serogroup C meningococcal disease in a community outbreak setting and to evaluate potentially modifiable barriers to vaccination in an area with persistent meningococcal disease following immunization . DESIGN: Matched case-control study of vaccine efficacy using cases of serogroup C meningococcal disease in persons eligible for vaccination during mass vaccination campaigns . Control patients were matched by neighborhood and age . The control group was used to identify possible barriers to vaccination . SETTING: Gregg County, Texas, population 106076, from 1993 to 1995 . PARTICIPANTS: A total of 17 case patients with serogroup C meningococcal disease eligible for vaccine and 84 control patients . MAIN OUTCOME MEASURES: Vaccine efficacy and risk factors associated with nonvaccination . RESULTS: Vaccine efficacy among 2- to 29-year-olds was 85% (95% confidence interval, 27%-97%) and did not change in bivariate analyses with other risk factors that were significant in univariate analysis . Among control patients, older age was strongly associated with nonvaccination; vaccination rates for 2- to 4-year-olds, 5- to 18-year-olds, and 19- to 29-year-olds were 67%, 48%, and 20%, respectively (chi2 for linear trend, P=.01) . CONCLUSIONS: The meningococcal polysaccharide vaccine was effective against serogroup C meningococcal disease in this community outbreak . Although specific barriers to vaccination were not identified, older age was a risk factor for nonvaccination in the target population of 2- to 29-year-olds . In future outbreaks, emphasis should be placed on achieving high vaccination coverage, with special efforts to vaccinate young adults.

J Infect Dis, 1998 Feb, 177(2), 497 - 500
New Zealand epidemic of meningococcal disease identified by a strain with phenotype B:4:P1.4; Martin DR et al.; New Zealand is experiencing an epidemic of serogroup B meningococcal disease, which has taken the rate of disease from an average of 1.5/100,000 population in the preepidemic years of 1989 and 1990 to 14.0/100,000 in 1996 . Sterile-site isolates of Neisseria meningitidis from cases of invasive disease have been phenotypically characterized by serogrouping, serotyping, and serosubtyping, revealing the involvement of a strain with phenotype B:4:P1.4 . Macrorestriction analysis using pulsed-field gel electrophoresis on 667 meningococci isolated from cases during the epidemic has identified the clonal relationship of meningococci expressing the PorA P1.4 antigen . Multilocus enzyme electrophoresis has shown the epidemic strain B:4:P1.4 to belong to lineage III . The recorded characteristics of New Zealand's epidemic are consistent with previous serogroup B epidemics in other parts of the world.

J Antimicrob Chemother, 1997 Dec, 40(6), 895 - 7
Meropenem susceptibility of Neisseria meningitidis and Streptococcus pneumoniae from meningitis patients in The Netherlands; van de Beek D et al.; In-vitro susceptibility of 299 Neisseria meningitidis and 157 Streptococcus pneumoniae strains from meningitis patients in The Netherlands in 1993 and 1994 to meropenem was determined using the Etest . Susceptibility to penicillin, ceftriaxone, and chloramphenicol was also determined . Rifampicin susceptibility was additionally tested for N . meningitidis . Of the meningococci, 4.3% were of intermediate resistance to penicillin and 0.3% were resistant to rifampicin . One pneumococcal isolate (0.6%) was of intermediate resistance to penicillin . All strains were susceptible to meropenem . We conclude that meropenem is in vitro highly active against N . meningitidis and S . pneumoniae.

Heart Lung, 1997 Nov-Dec, 26(6), 492 - 500
Case study of fulminant meningococcal septicemia diagnosed in a twenty-year-old woman with bulimia nervosa; Pierson DM; Fulminant meningococcal septicemia accounts for 5% to 10% of patients with meningococcemia; it is rapidly progressive and is associated with high morbidity and mortality rates . The highest meningococcal incidence is found in the 6- to 20-month-old age group; whereas immunoincompetence is suggested in adults with the condition . Coincidentally, eating disorders are purported to be the most prevalent psychiatric or behavioral disturbance affecting adolescents, and studies indicate that vulnerability to infectious disease may be present in this group as a result of a subclinical malnutrition state . I report a case of fulminant meningococcal septicemia in a patient with a comorbid eating disorder of bulimia nervosa, who had a tumultuous disease course, and with rapid and aggressive management of her condition--an impressive recovery.

Zh Mikrobiol Epidemiol Immunobiol, 1995 Jul-Aug, (4), 67 - 71
{The relationship between the immunological efficacy of a dried meningococcal group-A polysaccharide vaccine and the molecular parameters of the group-A polysaccharide}; Alliluev AP et al.; This work deals with the problem of relationship between the molecular parameters of group A meningococcal polysaccharide and its immunological effectiveness for laboratory animals and humans . The depolymerization of group A polysaccharide contained in the vaccine leads to a decrease in its capacity of inducing the production of hemagglutinating (19S and 7S) and bactericidal IgA antibodies in humans, as well as inducing an increase in the number of cells producing IgA antibodies in the spleen of immunized mice and the appearance of circulating IgA antibodies in their sera . As shown in this investigation, fully developed immune response to group A meningococcal vaccine may be achieved in humans only if the content of group A high-molecular polysaccharide in the vaccine is not less than 70% . Mice have been recommended as an experimental model for the prognostication of the effectiveness of meningococcal polysaccharide vaccines and for their control in the process of manufacture instead of currently used titration of bacteriolysins in the sera of immunized humans.

Zh Mikrobiol Epidemiol Immunobiol, 1995 Jul-Aug, (4), 17 - 9
{The range of individual sensitivity to adhesion by Neisseria meningitidis serogroup B in young men}; Rumiantsev SN et al.; 5,340 young adult males, including 5,149 healthy persons, 141 N . meningitidis carriers, 25 patients with generalized meningococcal infection and 6 patients with nasopharyngitis of meningococcal etiology, were examined . The study revealed that red blood cells of 17.4% of healthy persons were highly sensitive to N.meningitidis adhesion (adhesion indices equal to 0.25 and less), red blood cells of 20.4% of persons had low sensitivity to N.meningitidis adhesion (adhesion indices equal to 2 and greater) . All other persons with high sensitivity of their red blood cells proved to be patients with meningococcal infection or carriers of N.meningitidis of the same group.

Lik Sprava, 1996 May-Jun, (5-6), 136 - 41
{Oculomotor disorders in the clinical picture of bacterial meningoencephalitis}; Iarosh O et al.; The clinical study comprising 254 patients with bacterial meningoencephalitis (meningococcal, pneumococcal, staphylococcal, undefined, with n = 135, 76, 43, 120 respectively) permitted identifying a syndrome of oculomotor disturbances . It has been shown that assessment of changes in oculomotor disturbances enables the extent of inflammatory process, focal lesion as well as course and outcome of bacterial meningoencephalitis to be determined in a timely fashion.

Rev Neurol, 1997 Sep, 25(145), 1381 - 2
{Spontaneous intracranial hemorrhages in childhood}; Veira C et al.; INTRODUCTION: Spontaneous or non-traumatic intracranial haemorrhages seen in children of under 15 years old are most frequently due to cerebral vascular malformations, followed at a considerable distance by blood disorders, vasculopathies, tumours and the complications of radio-therapy . OBJECTIVE: To present the cases of spontaneous and non-traumatic cerebral haemorrhage seen at our hospital . MATERIAL AND METHODS: We reviewed all the paediatric cases of spontaneous cerebral haemorrhage diagnosed in our hospital over the previous sixteen years, excluding bleeding in the neonatal period . Computerized tomography was done in all cases, study of the cerebrospinal fluid, angiography and/or magnetic resonance in some cases . RESULTS: We selected 44 patients, of who the aetiology could be determined in 30 . Of these, 20 cases were due to vascular malformations, 7 were associated with haematological disorders, 2 with cerebral tumours and one case with meningococcal sepsis . The commonest form of presentation was that of an acute intracranial hypertension syndrome, also showing focal deficits, partial crises and meningism . CONCLUSIONS: The commonest cause of spontaneous intracranial haemorrhage in children is due to rupture of a vascular malformation, namely an arterio-venous malformation . Angiography and/or magnetic resonance are the techniques of choice for diagnosis . The various causes of disorders of haemostasia also are important in giving rise to intracranial bleeding.

Cent Eur J Public Health, 1997 Dec, 5(4), 214 - 8
Development of the epidemiological situation in invasive meningococcal disease in the Czech Republic caused by emerging Neisseria meningitidis clone ET-15/37; Krizova P et al.; Meningococcal clone ET-15/37, which appeared as a new one in the Czech Republic in 1993, caused an emergency epidemiological and clinical situation in invasive meningococcal disease, characterized by a high fatality rate (20%) compared to the "normal" fatality rate due to "non ET-15/37" strains . Morbidity rate increased since the first year of the new clone occurrence and reached the peak in 1995 . This clone has spread all over the country and investigation of the epidemiological markers of Neisseria meningitidis allowed to quickly recognize the emergency situation and subsequently to provide a targeted vaccination with A + C polysaccharide meningococcal vaccine which prevented the spread of the disease caused by Neisseria meningitidis C . The most frequent phenotype of ET-15/37 clone was C:2a:P1.2(P1.5) and its percentage achieved 80% of group C Neisseria meningitidis strains tested . This antigenic shift of Neisseria meningitidis was associated with the age shift in invasive meningococcal disease morbidity: teenagers started to be the most affected age group and later age group of 1-4 olds followed with high morbidity rates . In 1995 B variant of ET-15/37 clone, B:2a:P1.2(P1.5), appeared, causing a high fatality rate, too . Some data are indicative of a possible decrease in the invasive meningococcal disease incidence in the Czech Republic; nevertheless, the active surveillance and detailed investigation of meningococci have to be continued . After four years following the vaccination and chemoprophylaxis strategy recommended in the Guidelines, set up by the National Reference Laboratory for Meningococcal Infections in 1993, it is possible to conclude, that there have been practically no secondary cases of invasive meningococcal disease in the Czech Republic.

Commun Dis Rep CDR Rev, 1997 Dec 12, 7(13), R195 - 200
A retrospective survey of clusters of meningococcal disease in England and Wales, 1993 to 1995: estimated risks of further cases in household and educational settings; Hastings L et al.; Information about the epidemiology of meningococcal disease case clusters and the risk of further cases is sparse . Data on clusters in household and educational settings from 1 January 1993 to 31 March 1995 was requested from consultants in communicable disease control in England and Wales through a retrospective postal survey . Ninety-three per cent (122/131) responded . Of the 114 cases in 45 reported clusters, 77 (67.5%) were microbiologically confirmed . The case fatality rate in index cases was higher than in associated cases (18.2% vs 4.5%; p = 0.02) . Five out of 11 clusters in household settings consisted only of index and co-primary cases . No further cases occurred within two weeks after giving chemoprophylaxis to household contacts . The relative risks of further cases in the week after the index case arose were estimated to be 1200 for contacts in the household, 160 in secondary schools, 60 in primary schools, 1.8 in universities/colleges, and 0 in nurseries . Between seven and 30 days the relative risks were lower; 150 in households, and between 0 and 13 in all other settings . Beyond 30 days, the relative risk in the household setting was 8 and lower than this in all other settings . The absolute risk of further cases in the month following the index case was calculated as 210 per 100,000 in household members, 7-10/10(5) in pupils at the same school, and 0.6/10(5) in students at the same university or college . The current policy in England and Wales to recommend chemoprophylaxis for household members may prevent half of the further cases in this setting . Raised awareness may have contributed to the lower case fatality rate among household contacts who developed meningococcal disease, but the number of co-primary cases observed should prompt urgent enquiries about current illness in household contacts of index cases . The relative risk of further cases in preschool groups was low and apparently unaffected by changes in chemoprophylactic policy . The relative risk in school settings was raised in the month following a case, but the absolute risk was still low . Further study to quantify the risk in university settings is needed.

Arkh Patol, 1997 Sep-Oct, 59(5), 22 - 7
{Kidney morphology in children with meningococcal infection}; Khodasevich LS et al.; The kidneys of 30 children aged 1 month to 5 years who died of meningococcal infection were studied . Three variants of the kidney damage were distinguished on the basis of morphometric parameters . These variants corresponded to the stages of the infectious-toxic shock . The 1st variant observed in the reversible shock stages was characterized by arteriolar spasm and circulation shunts . The 2nd variant corresponded to initial manifestations of the disseminated vascular coagulation and was characterized by a combination of spasm and paralytic arteriola dilatation with a predominant thrombosis of the juxtamedullar glomeruli . The 3rd variant, the stage of the organ alterations, was followed by development of glomerular thrombotic microangiopathy with tubular epithelial necrosis in the proximal tubules this being the morphological counterpart of the hemolytico-uremic syndrome.

Klin Padiatr, 1997 Nov-Dec, 209(6), 380 - 3
{Recombinant tissue plasminogen activator in treatment of fulminant meningococcal infection}; Winter K et al.; This article reports about a young boy with fulminant meningococcal septicemia . Conventional treatment with antibiotics, intensive care and hemostatic drugs hold up vital functions . Because of extensive purpura fulminans with skin necrosis recombinant tissue plasminogen activator (rt-PA) was used . Under this therapy clinical improvement was observed.

Mol Gen Genet, 1997 Dec, 257(1), 28 - 34
Molecular divergence of the sia locus in different serogroups of Neisseria meningitidis expressing polysialic acid capsules; Claus H et al.; The serogroups B, C, W135 and Y of Neisseria meningitidis express chemically and immunologically distinct capsular polysaccharides containing sialic acid . In the case of serogroup B meningococci sialic acid is synthesized by the gene products of a locus termed sia and forms the homopolymers of the capsule . The organization of the genes required for sialic acid synthesis in serogroups B, C, W135 and Y was elucidated by PCR technology . Cloning, sequencing and the functional expression of the polysialyltransferase (PST) genes of serogroups B and C demonstrated that the difference in capsule composition derives from the presence of related, but distinct siaD genes coding for PSTs . Analysis of meningococci of serogroups W135 and Y expressing sialic acid heteropolymers revealed that the DNA sequences of the corresponding genetic loci in these serogroups were highly homologous, but differed completely from the siaD genes of serogroups B and C . This finding suggests that enzymes unrelated to those of serogroups B and C are required for the formation of sialic acid heteropolymers characteristic of the capsules of serogroups W135 and Y.

Curr Opin Hematol, 1995 Sep, 2(5), 402 - 6
Disseminated intravascular coagulation; Kitchens CS; Disseminated intravascular coagulation is the result of a severe underlying disorder that initiates massive activation of the coagulation system . It is always a symptom of the underlying disorder . These disorders may be as varied as meningococcemia and abdominal aortic aneurysm . Disseminated intravascular coagulation is a clinical diagnosis . Once the clinical impression has been considered, a small number of readily available tests will substantiate the diagnosis . Further testing is probably not necessary and certainly not cost-effective . Therapy for disseminated intravascular coagulation requires 1) the correction of the underlying problem, either by drainage of an abscess for sepsis, evacuation of the uterus in an obstetric catastrophe, or treatment of septicemia with antibiotics; and 2) the concomitant restoration of the circulatory system, perfusion, blood pressure, and electrolyte balance . Other forms of therapy are available but are quite secondary to these two . Success depends on the ability to recognize and correct the cause.

J Intern Med, 1997 Dec, 242(6), 519 - 20
The usefulness of skin culture in the diagnosis of chronic meningococcaemia; Texereau M et al.; We deal with the second reported case of chronic meningococcaemia in which the culture of skin biopsy led to the diagnosis . A 46-year-old man presented a history of recurrent fever and rash . Laboratory studies revealed an inflammatory syndrome . Serologic tests as well as blood culture tests were negative . The histological examination of skin lesions revealed a perivascular infiltrate in the dermis without any picture of leukocytoclastic vasculitis . A culture of skin specimen tested positive for Neisseria meningitidis (N . meningitidis) . After a week of antibiotic treatment, the patient recovered with no recurrence of either fever or rash over a two year period.

J Intern Med, 1997 Dec, 242(6), 455 - 64
Hypocomplementaemia caused by C3 nephritic factors (C3 NeF): clinical findings and the coincidence of C3 NeF type II with anti-C1q autoantibodies; Skattum L et al.; OBJECTIVES: The main purposes were to document manifestations associated with prolonged or clinically unexplained C3 deficiency and to approximate how often hypocomplementaemia of this kind is caused by C3 nephritic factors (C3 NeF), i.e . autoantibodies to alternative pathway C3 convertases . We also wished to distinguish between C3 NeF types I and II and to assess coincident autoantibody responses to the collagen-like region of C1q (C1qCLR) . SETTING: The investigation was based on serum samples referred to a specialized laboratory for complement analysis in the course of several years . SUBJECTS: Twenty-five persons with C3 concentrations lower than 0.43 g L-1, a third of the normal, were included in the study . RESULTS: Analysis using three methods provided evidence of C3 NeF in 20 persons with equal frequencies of C3 NeF types I and II . We also gave evidence of antibody specificity differences for the two types of C3 NeF . Six patients with C3 NeF type II showed antibodies to C1qCLR . Membranoproliferative glomerulonephritis was the predominant diagnosis and two patients had partial lipodystrophy reflecting the well-known association between these diseases and C3 NeF . Anaphylactoid purpura, systemic lupus erythematosus, and severe infection, mainly meningococcal disease, were also observed . CONCLUSIONS: The study group was probably fairly representative of C3 deficiency syndromes as encountered in clinical practice . The findings emphasize the heterogeneity of C3 NeF, and that acquired C3 deficiency syndromes caused by C3 NeF should perhaps be considered more often in diagnostic work.

Presse Med, 1997 Oct 25, 26(32), 1516 - 9
{Rapid epidemiological characterization of Neisseria meningitidis using polymerization chain reaction from biological samplings}; Giorgini D et al.; OBJECTIVES: Due to the spread of the meningococcal infections, a good epidemiological surveillance is needed . Prophylactic measures should be undertaken because of the high transmissibility of these bacteria . One problem which hinders the epidemiological characterization is that the responsible strain should be isolated . The aim of this work is to develop a rapid and non culture typing method of Neisseria meningitidis . METHODS: Six cerebrospinal fluids were obtained from 5 different patients with meningococcal meningitis . A specific locus, pil A, for N . meningitidis was amplified by polymerization chain reaction (PCR) . The polymorphism of this locus was then analyzed by digesting the PCR products with one of three different restriction enzymes . RESULTS: The polymorphism of this locus allowed us to establish the clonal relationships between the meningococcal strains involved in the infection . Three CSF corresponded to epidemiological strains . CONCLUSION: This typing method allows a rapid and less expensive epidemiological characterization of meningococcal infections . Moreover, it is a non culture typing method.

Scand J Infect Dis, 1997, 29(5), 479 - 83
Purpura fulminans in pneumococcal sepsis: case report and review; Carpenter CT et al.; Purpura fulminans is classically defined by ecchymotic skin lesions, fever, and hypotension . The majority of cases occur in association with bacterial sepsis, and disseminated intravascular coagulation (DIC) is usually present . Prompted by our experience with a patient with pneumococcal sepsis and purpura fulminans in whom hypotension was never observed, we evaluated the important parameters of sepsis in reports of this syndrome . 42 additional cases of pneumococcal bacteremia and purpura fulminans were identified . Hypotension was present in only 51% . Although DIC was present in 85% of patients, hypofibrinogenemia was documented in only 26% . By contrast, both hypotension and hypofibrinogenemia are present in the vast majority of patients described with purpura fulminans in association with meningococcal sepsis . These data confirm that hypotension is not a necessary feature of the syndrome of purpura fulminans associated with pneumococcal sepsis and suggest further that qualitative or quantitative differences exist in the DIC cascade of pneumococcal vs meningococcal sepsis.

J Laryngol Otol, 1997 Oct, 111(10), 913 - 6
Acute otitis media and otitis media with effusion in children with bacterial meningitis; Richardson MP et al.; Acute otitis media and otitis media with effusion (OME) have often been observed in children with bacterial meningitis . OME has also been proposed as the mechanism of reversible hearing loss after meningitis . In this controlled study, children with acute bacterial meningitis were studied using auditory brainstem responses (ABR), otoacoustic emissions, tympanometry and otoscopy . An age- and sex-matched control was recruited for each patient and the incidence of acute otitis media and OME was compared between the two groups . One hundred and twenty-four children with meningitis were studied . Ninety-two children (74 per cent) had meningococcal meningitis . Five patients (4 per cent) had conductive hearing loss (ABR threshold > or = 30 dB HL) at the time of discharge from hospital . None of the patients or controls had acute otitis media . Patients and controls were well matched for risk factors for OME and the prevalence of middle ear effusion in patients and controls was 7.2 per cent and 11.3 per cent respectively . The relative risk of OME in the children with meningitis was 0.64 (95 per cent confidence interval 0.29 to 1.42) . After nine months, three of the five children with meningitis and conductive hearing loss had regained normal hearing . In contrast to previous reports, there was no relationship between bacterial meningitis and acute otitis media or OME in this study . Nevertheless, coincidental conductive hearing defects were identified as the cause of reversible hearing loss in three patients.

Enferm Infecc Microbiol Clin, 1997 Oct, 15(8), 414 - 7
{A clone of Neisseria meningitidis serogroup C was responsible in 1994 of an unusual high rate of strains with a moderate resistance to penicillin in Caracas (Venezuela)}; Toro S et al.; BACKGROUND: The aim of the study was to analyse meningococcal strains isolated from patients in Caracas (Venezuela) with epidemiological markers and to determine their susceptibility to antimicrobial agents . METHODS: We analyzed 29 meningococcal clinical strains isolated during 1994 in Caracas by serogrouping, serotyping and subserotyping, multilocus enzyme analysis (MEE), ribotyping and pulse field electrophoresis (PFGE) profile . We also determined the Minimal Inhibitory Concentration (MIC) to 5 antimicrobial agents . RESULTS: Twenty four (82.7%) were group C meningococcal strains . All group C meningococci were characterized as C: 2b: P1.5, belonging to the same electrophoretic type (ET) by MEE and showing the same profile by PFGE by using Bg/II endonuclease restriction enzyme . These group C meningococci showed two different patterns by ribotyping, with only one band difference . All Group C and one group B N . meningitidis isolates were moderately resistant to penicillin (MIC > or = 0.12 mg/l) . CONCLUSIONS: During 1994 an unusual high incidence of meningococcal strains moderately resistant to penicillin (PenMR) was detected in Caracas (Venezuela) . A clone of C: 2b: P1.5 meningococci seem to be responsable for this high incidence of PenMR isolates.

Infect Immun, 1998 Jan, 66(1), 213 - 7
Periplasmic superoxide dismutase in meningococcal pathogenicity; Wilks KE et al.; Meningococcal sodC encodes periplasmic copper- and zinc-cofactored superoxide dismutase (Cu,Zn SOD) which catalyzes the conversion of the superoxide radical anion to hydrogen peroxide, preventing a sequence of reactions leading to production of toxic hydroxyl free radicals . From its periplasmic location, Cu,Zn SOD was inferred to acquire its substrate from outside the bacterial cell and was speculated to play a role in preserving meningococci from the action of microbicidal oxygen free radicals produced in the context of host defense . A sodC mutant was constructed by allelic exchange and was used to investigate the role of Cu,Zn SOD in pathogenicity . Wild-type and mutant meningococci grew at comparable rates and survived equally long in aerobic liquid culture . The mutant showed no increased sensitivity to paraquat, which generates superoxide within the cytosol, but was approximately 1,000-fold more sensitive to the toxicity of superoxide generated in solution by the xanthine/xanthine oxidase system . These data support a role for meningococcal Cu,Zn SOD in protection against exogenous superoxide . In experiments to translate this into a role in pathogenicity, wild-type and mutant organisms were used in an intraperitoneal mouse infection model . The sodC mutant was significantly less virulent . We conclude that periplasmic Cu,Zn SOD contributes to the virulence of Neisseria meningitidis, most likely by reducing the effectiveness of toxic oxygen host defenses.

Ren Fail, 1997 Nov, 19(6), 807 - 10
Outcome of acute renal failure in meningococcemia; Marotto MS et al.; We studied 28 consecutive patients (18 males and 10 females), 1-32 years of age, admitted to the intensive care unit from January 1989 to July 1995, with acute renal failure (ARF) due to meningococcal septicemia . All patients were treated with dexamethasone, penicillin, and/or chloramphenicol . Twenty-two patients presented septic shock and needed fluid replacement and vasoactive drugs . Acute renal failure was oliguric in 67.8% . Maximum levels of blood urea and serum creatinine were 210.3 +/- 26.6 mg/dL and 6.9 +/- 1.3 mg/dL, respectively . Metabolic acidosis was observed in 89.3% and hyperkalemia in 43% . The fractional excretion of sodium on day 1 was high (9.9 +/- 0.6%) . The urinalysis did not show trace protein, but hematuria was positive in 81% . The mortality rate was 63.3% . In the 10 survivors, oliguria was present for a period of 12.7 +/- 2.4 days, and the period to reach a normal serum creatinine level was 20.2 +/- 4.7 days, although in two female patients, 7 and 17 years old, the elevated serum creatinine persisted . Renal biopsy was performed in one of these patients which revealed bilateral cortical necrosis . These data show that acute renal failure in meningococcemia presents high mortality rate associated to shock; 80% of the survivors recover renal function; and bilateral cortical necrosis occurred in one patient in this series.

Enferm Infecc Microbiol Clin, 1997 Aug-Sep, 15(7), 369 - 72
{Meningococcal infection caused by Neisseria meningitidis serogroup C}; Ursua MI et al.; BACKGROUND: In recent years an increase has been observed in the prevalence of meningococcal infection by Neisseria meningitidis serogroup C and in the appearance of strains with moderate resistance to penicillin . PATIENTS AND METHODS: A microbiologic study of the cases of meningococcal infection of serogroup C treated from 1995 to 1996 in the health care area of Ferrol (La Coruna, Spain) was carried out . RESULTS AND CONCLUSIONS: Twenty-nine cases were detected in 1995 and 28 in 1996 . Meningococcal infection was observed in patients ranging from 8 months to 21 years of age (mean 5.7 years) . Distribution by sex was homogeneous . Two patients died . According to the clinical presentation, 11 were sepsis (38%), 4 meningitis (14%) and 14 both processes (48%) . In 4 LCR samples, the analytical study was normal with posterior positive culture results . The detection of bacterial antigen by latex agglutination in CSF only detected 32% of the cases . MIC study determined that 11 strains (38%) presented moderate resistance to penicillin, 9 with a MIC of 0.12 microgram/ml, one with a MIC of 0.25 microgram/ml and another with a MIC of 0.5 microgram/ml . In all the cases the strains were sensitive to cefotaxime (MIC < or = 0.06 microgram/ml) and rifampicin (MIC < or = 0.5 microgram/ml) . All the strains belonged to serogroup C serotype 2b, serosubtype P1.2,5 . During the study period 4 additional cases of meningococcal disease by serogroup B were observed.

Acad Emerg Med, 1997 Dec, 4(12), 1129 - 36
Adverse outcomes of managed care gatekeeping; Young GP et al.; OBJECTIVES: To determine whether telephone preauthorization for reimbursement of ED care (medical "gate-keeping") by managed care organizations (MCOs) is associated with adverse outcomes . METHODS: A structured review was performed of case reports solicited during 1994 and 1995 with possible adverse outcomes related to managed care gatekeeping . Gatekeeping was defined as the requirement imposed by an MCO that ED staff contact on-call gatekeepers (i.e., clinical or nonclinical MCO personnel) to request preauthorization for ED treatment (a requirement that such MCOs enforce by refusing payment for the ED care unless preauthorization is obtained) . Cases in which gatekeeper denial of preauthorization occurred were sought . Two physicians agreed on patient eligibility and classification criteria, then independently, retrospectively classified case reports identified as MCO ED payment denials into 1 of 4 categories: 1) adverse outcome; 2) patient placed at increased risk of death or disability; 3) "near miss" (emergency physicians prevented adverse outcome by caring for patient despite denial); and 4) none of the above . RESULTS: Of the 143 cases reviewed, 29 reports represented MCO ED payment denial . Of these 29 eligible cases, there were 4 (14%) patients with adverse outcomes, 4 (14%) patients placed at increased risk, and 21 (72%) near misses . All of the 29 cases came from different EDs, representing 9 different states, with the majority from California . Adverse outcomes included respiratory failure from fulminant meningococcemia, hypovolemic syncope from ruptured ectopic pregnancy, hypovolemic arrest from vascular fibroid hemorrhage necessitating emergency hysterectomy, and prolonged postoperative course following ruptured duodenal ulcer . Patients placed at increased risk were diagnosed as having epiglottitis, myocardial infarction, ruptured ectopic pregnancy, and delayed treatment of hip septic arthritis . Near misses included diagnoses of ectopic pregnancy (n = 2), pneumothorax (n = 2), alcohol withdrawal seizures and pancreatitis necessitating intensive care unit admission, appendicitis, bacterial meningitis, cerebrovascular accident, cryptococal meningitis in immuno comprised host, endocarditis, incarerated inguinal hernia, meningocococemia, meninoccocal meningitis, peritonsillar abscess, pneumococcal meningitis, ruptured abdominal aortic aneurysm, shock from gastrointestinal bleeding, small bowel obstruction, schizophrenic crisis resulting in psychiatric hospitalization, suicidal depression resulting in psychiatric hospitalization, and unstable angina . CONCLUSION: Adverse outcomes occur with MCO gatekeeping, Although the present study cannot ascertain whether this is a frequent event or a rare one, the safety of MCO gatekeeping deserves further study.

Thorax, 1997 Oct, 52(10), 927 - 9; discussion 926-7
Three cases of meningococcal pneumonia; Jones EM et al.; Three cases of pneumonia due to Neisseria meningitidis are described . In all three cases the organism was isolated only from blood cultures, but in the presence of good clinical and radiological evidence of pneumonia . The isolates belonged to three different serogroups: B type 2b, C, and Y . The cases illustrate the fact that N meningitidis can cause pneumonia and that culture of blood plays an important part in the diagnosis . Clinically there is nothing to differentiate meningococcal pneumonia from other causes of community acquired pneumonia . Predisposing factors include aspiration, immunosuppression, influenza, and adenovirus infections . When diagnosed, pneumonia due to N meningitidis should be notified and prophylaxis given as for meningitis or septicaemia.

Med Microbiol Immunol (Berl), 1997 Oct, 186(2-3), 159 - 66
Functional characterization of an isogenic meningococcal alpha-2,3-sialyltransferase mutant: the role of lipooligosaccharide sialylation for serum resistance in serogroup B meningococci; Vogel U et al.; The neisserial alpha-2,3-sialyltransferase, which is encoded by the lst gene, terminally links sialic acid to the lacto-N-neotetraose residue of neisserial lipooligosaccharide (LOS) . We used the recently published nucleotide sequence of the neisserial lst gene to construct an isogenic serogroup B meningococcal lst mutant by insertion of a kanamycin resistance gene . The resulting lst mutant expressed the unsialylated lacto-N-neotetraose structure . Using bactericidal assays and an infant rat model of meningococcal infection, we were able to demonstrate that lst mutation, in contrast to galE mutation, which results in a truncated LOS, or to siaD mutation, which results in loss of the capsule, neither had an effect on resistance to normal human serum, nor did it impair the ability of meningococci to spread systemically in the non-immune host . The lst mutant was serum resistant despite of the fact that the central factor of complement activation, C3b, was deposited on the lst mutant as efficiently as it was on the galE mutant . Thus, the terminal sialic acid residue linked to the wild-type LOS inhibited C3b deposition on the meningocuccus . However, in contrast to the galE mutant, where C3b deposition is promoted by IgM binding, the lst mutant's surface is not a target for IgM molecules . Thus, the lacto-N-neotetraose residue of neisserial LOS alone, without the presence of terminal sialic acid, is sufficient to block IgM epitopes either on the LOS itself, or on other surface molecules . Our data provide further insight into the complex interplay of capsular and LOS sialic acids in serogroup B meningococci with host effector mechanisms, and suggest that LOS sialylation in meningococci is of a less central importance as it is in gonococci.

Acta Paediatr, 1997 Nov, 86(11), 1263 - 6
Severe skin loss after meningococcal septicaemia: complications in treatment; Huang S et al.; Meningococcal septicaemia can lead to purpura fulminans with subsequent full thickness skin loss and deep muscle damage . The case reports on two infants who recovered from such a severe episode are used to describe post-septicaemic procedures and complications encountered in nursing care, psychological support and rehabilitation, with the main focus on surgery . Skin grafting is complicated by contaminated and contracting wound areas . Extensive tissue necrosis required leg amputations . Cultured keratinocytes in one of the patients were found to be too vulnerable . It has still to be proven whether more radical early-stage fasciotomies can limit skin and muscle necrosis . Patients with meningococcal septicaemia are subject to a high number of complications that are optimally treated in a burns unit . These patients require up-to-date knowledge of constantly evolving treatment possibilities and a high-level collaboration of all medical fields involved.

J Clin Microbiol, 1997 Dec, 35(12), 3215 - 9
Confirmation of suspicious cases of meningococcal meningitis by PCR and enzyme-linked immunosorbent assay; Saunders NB et al.; A significant problem in efficacy trials of meningococcal vaccines has been accurate identification of all cases of meningococcal disease that occur in study populations . The accuracy of case determination would be improved by utilizing methods which confirm or disprove suspicious cases of meningococcal disease that are culture negative . A collection of serum and cerebrospinal fluid (CSF) samples from a meningococcal vaccine field trial performed in Iquique, Chile, were utilized to assess the status of patients for whom cultures, Gram stains, and clinical evaluations for meningococcal disease were available . Nested PCRs (nPCRs) for amplification of Neisseria meningitidis DNA in CSF samples and enzyme-linked immunosorbent assays (ELISAs) for quantification of serum immunoglobulin G antibodies specific for N . meningitidis were used in combination to confirm or eliminate cases classified by physicians as suspicious for meningococcal disease . Samples from 12 of 79 patients suspected of having meningococcal meningitis tested positive by both methods; specimens from 61 of the 79 were negative by both methods; and samples from 6 patients yielded ambiguous results, and these cases remained unconfirmed . Direct sequence analysis of amplified DNA from patients suspected of having meningococcal disease confirmed that 2 of the 12 newly confirmed cases were not attributable to the typical epidemic strain (B:15:P1.{7},3) while the others were due to the epidemic strain . A combination of nPCR and ELISA reduced the number of suspicious cases in this study from 79 to 6, thereby improving the potential for assessment of vaccine efficacy . Molecular identification by nPCR in conjunction with immunological assessment of patient response could be considered diagnostic of disease in future testing of meningococcal vaccines to improve efficacy analyses.

FEBS Lett, 1997 Nov 10, 417(2), 253 - 9
Identification of potential ferric binding residues in the iron-binding protein of pathogenic Neisseria meningitidis through structure-based multiple sequence alignments; Gorinsky B et al.; The ferric iron-binding proteins of pathogenic Neisseria display structural and metal-binding properties characteristic of the transferrin family . In the absence of structural data for the ferric iron-binding proteins, spacial folding templates have been derived for the meningococcal protein from complete and partial structure-based multiple sequence alignments with structurally related proteins . The templates have been used to identify a number of potential iron-binding residues . These include four residues that are identical with the iron coordinating ligands of transferrin, but only two reside within equivalent structural elements.

FEMS Immunol Med Microbiol, 1997 Oct, 19(2), 159 - 67
Analysis of the human Ig isotype response to individual transferrin binding proteins A and B from Neisseria meningitidis; Johnson AS et al.; Subcapsular antigens, including transferrin binding proteins, are being considered as potential vaccines against serogroup B meningococci . This study examined the human isotype antibody responses in cases of meningococcal disease to meningococcal TbpA (transferrin binding protein A) and TbpB (transferrin binding protein B) from two strains (SD and B16B6) expressing high and low molecular mass TbpB respectively . TbpA isolated from both strains were recognised more frequently and higher durable ELISA absorbance values were detected than those detected against TbpB from either strain . These antibody responses to Tbps were independent of the infecting meningococcal strain type . The antibody response to the four proteins was highly variable between individuals and differed significantly against all four antigens . The variability of immune responses to each Tbp from the two strains suggests that a successful vaccine would need to include TbpA and TbpB from a number of strains.

Infect Immun, 1997 Dec, 65(12), 5184 - 90
Human B- and T-cell responses after immunization with a hexavalent PorA meningococcal outer membrane vesicle vaccine; van der Voort ER et al.; The PorA protein from Neisseria meningitidis, a potential vaccine candidate, induces human bactericidal antibodies which are serosubtype specific . We developed a hexavalent PorA outer membrane vesicle vaccine based on reference strain H44/76 . This vaccine contains the six most prevalent PorA serosubtypes as found in many countries . We previously reported on the immune responses of 20 adult volunteers after a single immunization with this vaccine . In this study, the B- and T-cell responses in three adult volunteers were studied after three consecutive immunizations (0, 2, and 11 months) . The first immunization induced a strong B-cell response resulting in high immunoglobulin G levels in an outer membrane vesicle enzyme-linked immunosorbent assay . At least a fourfold increase in bactericidal activity was observed against the majority (four to six) of the vaccine antigens compared to prevaccination titers . Immunodominance was observed for one or two of the PorAs in the bactericidal assay with a set of six isogenic H44/76-derived PorA target strains . These strains carry the individual PorAs as present in the vaccine . The second and third immunizations did not induce a further increase in the immune responses . A decline in time with respect to PorA-specific antibodies was observed after each immunization . These observations were reflected by the T-cell proliferation responses . Two additional sets of isogenic H44/76-derived mutant strains were used to study the specificity and/or cross-reactivity of the induced bactericidal antibodies . These target strains differ only in expressing mutant family variants of either PorA P1.7,16 or P1.5,10, both present in the PorA vesicle vaccine . The bactericidal antibody responses found were directed predominantly against the P1.7 (loop 1 of P1.7,16) and the P1.10 (loop 4 of P1.5,10) epitopes . This indicates that different portions of PorA were involved in the induction of bactericidal antibodies depending upon the PorA serosubtype.

Lancet, 1997 Nov 29, 350(9091), 1590 - 3
Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans; Smith OP et al.; BACKGROUND: Inflammatory and coagulation processes are both affected in meningococcaemia . Severe acquired protein-C deficiency in meningococcaemia is usually associated with substantial mortality: in survivors, skin grafts, amputation, and end-organ failure are not uncommon . Protein C is a natural anticoagulant and also has important anti-inflammatory activity . We assessed the effects of early replacement therapy with protein-C concentrate together with continuous veno-venous haemodiafiltration and conventional treatment in meningococcaemia . METHODS: 12 patients aged between 3 months and 27 years with meningococcaemia and severe acquired protein-C deficiency (mean 0.20 IU/mL) were studied . All patients had septic shock, widespread purpura, skin necrosis, and disseminated intravascular coagulopathy . After a test dose of protein-C concentrate, patients received a continuous infusion with the dose adjusted daily to keep the plasma concentration between 0.8 and 1.2 IU/mL . 11 patients were given unfractionated intravenous heparin (10-15 IU kg-1 h-1) . Nine patients had haemodiafiltration and one had peritoneal dialysis . The Glasgow meningococcal septicaemia prognostic score and the paediatric risk of mortality score predicted a minimum mortality of 80% and 57%, respectively . FINDINGS: No patient died . No adverse reactions to the treatment were seen . Two patients had lower-limb amputations, one of whom had a thrombotic cerebrovascular accident; both patients had received the protein-C concentrate and heparin later than the rest of the group (60 h {16.97} vs 12 h {3.13}) . One patient developed chronic renal failure despite receiving protein-C infusion 15 h after admission . INTERPRETATION: The acquired severe deficiency of protein C in meningococcaemia contributes to the pathogenesis of the thrombotic necrotic lesions in the skin and other organs and probably has an important role in the inflammatory response . Protein-C therapy is merely one approach to improve the host response in this syndrome . We suggest that a double-blind, randomised, controlled multicentre trial is needed to confirm our results.

Lancet, 1997 Nov 15, 350(9089), 1439 - 43
Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis; Giroir BP et al.; BACKGROUND: Meningococcal sepsis remains an important cause of morbidity and mortality . We hypothesised that children with severe meningococcaemia might benefit from inhibition of the inflammatory processes thought responsible for fulminant disease . rBPI21 is a recombinant, N-terminal fragment of human bactericidal/permeability-increasing protein, which kills meningococci and binds to and clears bacterial endotoxin, these being the primary inducers of the systemic inflammation . The aim of this study was to determine the safety and kinetics of rBPI21 in children with severe meningococcaemia and to make a preliminary assessment of clinical outcome . METHODS: In this open-label, dose-escalation, phase I/II trial in severe meningococcaemia (Glasgow meningococcal prognostic septicaemia score {GMSPS} > or = 8), 26 patients aged 1-18 years, who had received their first dose of antibiotics no more than 8 hours earlier were given rBPI21 by infusion at total doses of 1.0, 2.0, and 4.0 mg/kg . FINDINGS: The patients had significantly raised plasma concentrations of bacterial endotoxin and cytokines . Peak and steady state BPI concentrations were comparable with pharmacokinetic data in healthy adults . All complications were compatible with the expected pattern for severe meningococcal sepsis . Only one patient died . This outcome was found to compare favourably with a predicted mortality of > or = 30% by GMSPS, > or = 15% by plasma endotoxin values, > or = 28% by plasma interleukin-6 concentrations, 29-49% by severity of coagulopathy, and 20% (11/54) by comparison with recent historical patients consecutively treated in participating centres before this study . INTERPRETATION: This, the first clinical trial or rBPI21, shows that rBPI21 can be safely administered to children with severe meningococcaemia and that the pharmacokinetics are consistent with patterns seen in healthy adults . Predicted mortality, on the basis of GMSPS, laboratory indices of inflammation and coagulopathy, and historical controls, was for between four and eight deaths . These findings have prompted a phase III randomised trial.

J Infect Dis, 1997 Nov, 176(5), 1285 - 92
Interaction of Neisseria maningitidis with the components of the blood-brain barrier correlates with an increased expression of PilC; Pron B et al.; A fatal untreated case of fulminant meningococcemia was examined to investigate the crossing of the blood-brain barrier (BBB) by Neisseria meningitidis . Microscopic examination showed bacteria in vivo adhering to the endothelium of both the choroid plexus and the meninges . Comparison of the isolates cultivated from the blood and the cerebrospinal fluid (CSF) revealed no antigenic variation of the pilin or the class 5 protein, whereas the expression of the PilC protein was greater in the CSF and the choroid plexus than in the blood . This was due to an increased activity of one of the pilC promotors . This higher expression of PilC correlated in vitro with greater adhesiveness to endothelial cells . A mutation in the single pilC locus of this strain abolished in vitro pilus-mediated adhesion to endothelial cells . These data suggest that PilC plays an important role in the crossing of the BBB, likely through pilus-mediated adhesion.

J Infect Dis, 1997 Nov, 176(5), 1277 - 84
Molecular epidemiology of sporadic (endemic) serogroup C meningococcal disease; Raymond NJ et al.; Understanding the basis of sporadic (endemic) meningococcal disease may be critical to prevention of meningococcal epidemic outbreaks and to understanding fluctuations in incidence . Active, prospective, population-based surveillance and molecular epidemiologic techniques were used to study sporadic serogroup C meningococcal disease in a population of 2.34 million persons (Atlanta area) . During 1988-1994, in which no outbreaks or case clusters were reported, 71 patients developed sporadic serogroup C meningococcal disease (annual incidence, 0.51/100,000) . Eighty-three percent of patients were >2 years old . By multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, and serotyping, 84% (52/62) of the isolates available for study were identical or closely related members of the electrophoretic type 37 (ET 37) complex responsible for multiple serogroup C outbreaks in the United States in the 1990s . Sporadic disease caused by 9 clonal strains occurred over periods up to 4 years and accounted for 45% (28/62) of cases . Sporadic serogroup C meningococcal disease was most often due to a limited number of related strains that appear to slowly circulate in the population.

Mil Med, 1997 Nov, 162(11), 769 - 72
Primary meningococcal arthritis: case report and review of the literature; Wells M et al.; Meningococcal arthritis is a recognized manifestation of Neisseria meningitidis infection, the presentation of which may be confusing . Although arthritis occurs in the setting of meningococcal meningitis, it may also be seen as a primary event without neurological involvement and with or without cutaneous manifestations . We describe a patient with primary meningococcal arthritis and review the literature relating to the clinical types and pathogenic mechanisms . Comparisons of patient series from 1980 to the present with those reported before 1980 are described.

Microbiologia, 1997 Sep, 13(3), 337 - 42
Moderate resistance to penicillin in Neisseria meningitidis; Saez Nieto JA et al.; Meningococcal moderate resistance to penicillin (MICs 0.12 to 1 mg/l) was rarely reported before the 1980's in Spain . The frequency of isolation of resistant strains increased from 0.4% in 1985 to 42.6% in 1990 . In the last few years, these strains have been reported in several countries, which suggests a change in the meningococcal response to penicillin . The resistance is due, at least in part, to a decreased affinity of penicillin binding protein 2 (PBP2) for penicillin . This decreased affinity has also been found in commensal Neisseriae . Population genetic studies demonstrate that recombinational events, replacing parts of the PBP2 gene by the corresponding regions of commensal species, followed by a rapid spread of the clones could be the origin of such resistant strains.

Infect Immun, 1997 Nov, 65(11), 4836 - 42
Interaction of Neisseria meningitidis with a polarized monolayer of epithelial cells; Pujol C et al.; An important step in the pathogenesis of Neisseria meningitidis is the crossing of two cellular barriers, one in the nasopharynx and one in the brain . To approach the mechanisms by which this bacterium can achieve these goals, we studied the interactions between N . meningitidis and a monolayer of polarized tight junction-forming T84 cells grown on filter units . A capsulated, piliated, Opa-, and Opc- N . meningitidis strain is shown to be capable of adhering to and crossing this monolayer several orders of magnitude more efficiently than an isogenic nonpiliated derivative . This bacterial interaction does not affect the barrier function of tight junctions, as assessed by (i) the absence of modification of the transepithelial resistance, (ii) the lack of increase of {3H}inulin penetration across the monolayer, and (iii) the absence of delocalization of ZO-1, a tight junction protein . Electron microscopy studies and confocal examinations demonstrated that N . meningitidis (i) induces cytoskeletal rearrangements with actin polymerization beneath adherent bacteria, (ii) is intimately attached to the apical membrane of the cells, and (iii) can be internalized inside cells . Immunofluorescent staining with antipilus antibodies showed evidence that meningococcal piliation was dramatically reduced at later time points of bacterial cell interaction compared to the early phase of this interaction . In addition, adhesive bacteria recovered from an infected monolayer are piliated, capsulated, Opa-, and Opc-, a phenotype similar to that of the parental strain . Taken together, these data demonstrate that following pilus-mediated adhesion, N . meningitidis is involved in an intimate attachment which requires a bacterial component different from Opa and Opc and that meningococci cross a monolayer of tight-junction-forming epithelial cells by using a transcellular pathway rather than a paracellular route.

Infect Immun, 1997 Nov, 65(11), 4436 - 44
Sialylation of Neisseria meningitidis lipooligosaccharide inhibits serum bactericidal activity by masking lacto-N-neotetraose; Estabrook MM et al.; Exogenous sialylation of gonococcal lipooligosaccharide causes resistance to serum bactericidal activity . The aim of this study was to determine how lipooligosaccharide sialylation affects the serum sensitivities of group C Neisseria meningitidis strains . The relationship between the degree of sialylation or expression of the lipooligosaccharide sialic acid acceptor, lacto-N-neotetraose (LNnT), of nine meningococcal strains and their sensitivities to a pool of normal human sera was assessed . All strains expressed LNnT that was variously endogenously sialylated . Susceptibility to serum bactericidal activity ranged from extremely sensitive to resistant in 50% serum . For endogenously sialylated strains, the amount of killing correlated with the amount of free LNnT above a threshold of expression; strains that expressed less than the threshold survived in 25% serum . All strains added more sialic acid when they were grown in medium that contained cytidine monophospho-N-acetylneuraminic acid . Exogenous sialylation reduced the expression of free LNnT and significantly increased serum resistance . Exogenous sialylation affected killing through both classical and alternative complement pathways . The killing of exogenously sialylated strains also correlated with the amount of free LNnT . The amounts of endogenous, exogenous, and total sialic acid bound to LNnT did not correlate with the resistance of strains to serum bactericidal activity; rather, the loss of free LNnT expression by sialylation was associated with resistance . In conclusion, the expression of free LNnT by group C meningococcal strains is directly associated with the amount of killing of organisms in pooled human sera . Both endogenous and exogenous lipooligosaccharide sialylation are associated with increased serum resistance by masking LNnT.

Mol Microbiol, 1997 Sep, 25(6), 1047 - 64
Clonal descent and microevolution of Neisseria meningitidis during 30 years of epidemic spread; Morelli G et al.; Serogroup A meningococci of subgroups III, IV-1 and IV-2 are probably descended from a common ancestor that existed in the nineteenth century . The 10.5kb sequences spanning five distinct chromosomal loci, encoding cell-surface antigens, a secreted protease or housekeeping genes and intergenic regions, were almost identical in strains of those subgroups isolated in 1966, 1966 and 1917 respectively . During the subsequent two to three decades, all of these loci varied as a result of mutation, translocation or import of DNA from unrelated neisseriae . Thus, microevolution occurs frequently in naturally transformable bacteria . Many variants were isolated only once or within a single geographical location and disappeared thereafter . Other variants achieved genetic fixation within months or a few years . The speed with which sequence variation is either eliminated or fixed may reflect sequential bottlenecks associated with epidemic spread and contrasts with the results of phylogenetic analyses from bacteria that do not cause epidemics.

BMJ, 1997 Sep 27, 315(7111), 774 - 9
Epidemiology and clinical management of meningococcal disease in west Gloucestershire: retrospective, population based study; Wylie PA et al.; OBJECTIVE: To study changes in the epidemiology and management of meningococcal disease in one health district during a period of high local incidence of disease . DESIGN: Prospective case ascertainment and data collection over 14 years, with retrospective analysis of cases . SETTING: West Gloucestershire (population 320,000) . SUBJECTS: Residents developing meningococcal disease between 1 January 1982 and 31 December 1995 . RESULTS: 252 cases of invasive meningococcal disease were identified, of which 102 (40%) were officially notified and 191 (76%) were confirmed by culture from a deep site . The observed disease incidence of 5.6/100,000/year was about 2.7 times the national incidence (as measured by either statutory notifications or reference laboratory reports) . The period 1983-90 was characterised by a prolonged localised outbreak due to serogroup B serotype 15 sulphonamide resistant (B15R) strains . General practitioners gave benzylpenicillin before hospital admission to 18% of patients who presented with meningococcal disease in the first half of the study period and to 40% who presented in the second half . The overall case fatality rate was 6.7% (17/252) . Four deaths were directly or indirectly related to lumbar puncture . Of 120 patients whose lumbar puncture yielded meningococci, nine (8%) showed no abnormality on initial examination . CONCLUSIONS: Neither laboratory records nor formal notifications alone can give an accurate estimate of the incidence of meningococcal disease . Because of the dangers of lumbar puncture, the frequency of misleading negative initial findings, and the advent of new diagnostic techniques, the need for samples of cerebrospinal fluid should be critically questioned in each case of suspected meningococcal disease.

Pediatr Infect Dis J, 1997 Oct, 16(10), 979 - 83
Tobacco smoke as a risk factor for meningococcal disease; Fischer M et al.; BACKGROUND: Since 1992 the US Pacific Northwest has experienced a substantial increase in the incidence of serogroup B meningococcal disease . The current meningococcal polysaccharide vaccine is poorly immunogenic in young children and does not protect against N . meningitidis serogroup B . Defining alternative approaches to the prevention and control of meningococcal disease is of considerable public health importance . METHODS: We performed a case-control study comparing 129 patients in Oregon and southwest Washington with 274 age- and area-matched controls . We used conditional logistic regression analysis to determine which exposures remained associated with disease after adjusting for other risk factors and confounders and calculated the proportion of disease attributable to modifiable exposures . RESULTS: After adjustment for all other significant exposures identified, having a mother who smokes was the strongest independent risk factor for invasive meningococcal disease in children < 18 years of age {odds ratio (OR), 3.8; 95% confidence interval (CI) 1.6 to 8.9)}, with 37% (CI 15 to 65) of all cases in this age group potentially attributable to maternal smoking . Adult patients were more likely than controls to have a chronic underlying illness (OR 10.8, CI 2.7 to 43.3), passive tobacco smoke exposure (OR 2.5, CI 0.9 to 6.9) and to smoke tobacco (OR 2.4, CI 0.9 to 6.6) . Dose-response effects were seen for passive smoke exposure and risk of disease in all age groups . CONCLUSION: Tobacco smoke exposure independently increases the risk of developing meningococcal disease.

Biochemistry, 1997 Oct 14, 36(41), 12583 - 91
Thermodynamic analysis of the interaction between a bactericidal antibody and a PorA epitope of Neisseria meningitidis; van den Elsen JM et al.; An antibody-peptide model system was used to study the binding characteristics between a bactericidal antibody (MN12H2) and the P1 . 16 epitope of class 1 outer membrane protein PorA of Neisseria meningitidis by means of a thermodynamic approach . A series of four linear peptides and three "head-to-tail" cyclic peptides (with ring sizes of 9, 15 and 17 amino acids) were synthesized and evaluated as ligands . The peptides contain a fluorescein label and the core determinant amino acid sequence TKDTNNN (residues 180-186) of the PorA P1.16 epitope of meningococcal strain H44/76 . Thermodynamic data of the binding of the peptide homologs of the epitope by MN12H2 were assessed by measuring affinity constants (Ka) over a temperature range of 4-55 degrees C, using fluorescence spectroscopy . Curvilinear plots of ln Ka versus T (K) revealed strong temperature dependencies of enthalpy (DeltaH) and entropy (DeltaS) . The Gibbs free energy change (DeltaG) was only weakly temperature dependent . The large negative enthalpy value indicated the importance of polar interactions in the binding of both linear and cyclic peptides by MN12H2 . Sturtevant's analysis of the thermodynamic parameters showed large unfavorable vibrational contributions to the binding for all linear peptides {Sturtevant, J . M . (1977) Proc . Natl . Acad . Sci.U.S.A . 74, 2236-2240} . The large hydrophobic contribution compensating these vibrational modes was partially attributed to aspecific interaction of the fluorescein label with the antibody . Binding of MN12H2 to conformationally restricted epitope sequences was characterized by a dramatic reduction in the size of unfavorable vibrational components of the thermodynamic parameters . Substitution of individual charged amino acids of the P1.16 epitope sequence revealed that aspartate-182 was essential for the binding . The pH profile observed for the MN12H2-peptide complexes with a midpoint pH of approximately 8.5 suggests a positively charged histidine from the antibody binding site to be involved in a charge interaction with Asp-182 . These findings are consistent with the results from the crystal structure of the Fab fragment of MN12H2 in complex with a linear fluorescein-conjugated peptide homolog of the P1.16 epitope {van den Elsen et al . (1997) Proteins (in press)}, thereby identifying the basis of an increased incidence of endemic disease in England and Wales since 1981 caused by a mutant meningococcal strain.

Clin Immunol Immunopathol, 1997 Nov, 85(2), 134 - 42
T-Cell epitope mapping the PorB protein of serogroup B Neisseria meningitidis in B10 congenic strains of mice; Delvig AA et al.; T-cell epitope mapping the meningococcal serotype 15 PorB protein performed in this study in three congenic strains of mice with B10 genetic background revealed at least three murine T-cell epitopes (55-72, 163-180, and 226-261), located in the highly conserved putative transmembrane regions of Neisserial porins . Proliferation assays with popliteal lymph node cells derived from mice immunized with the PorB protein or with synthetic 18-mer peptides showed that epitope 163-180 immunized only in the H-2d haplotype, epitope 55-72 could be presented by both H-2f and H-2s molecules, while the 226-261 region covered by three overlapping peptides could be efficiently recognized in context of all three MHC class II haplotypes studied . Inhibition experiments with blocking I-Aalpha- and I-Ealpha-specific mAb showed that peptide 163-180 was presented by I-Ad and peptide 244-261 was presented by both I-Af and I-As . In addition, evidence was obtained that peptide 226-243 was presented in context of H-2d or I-As haplotypes and peptide 55-72 was presented in context of I-Af and I-As loci . Finally, the Norwegian outer membrane vesicle vaccine, but not the purified PorB protein, could recall responses in mice immunized with synthetic peptides corresponding to the 226-261 region . Altogether, these results suggest that T-cell epitopes identified on the serotype 15 PorB protein, particularly those presented by several MHC class II molecules (e.g., 226-261), could have important implications for the development of meningococcal vaccines .

J Pediatr, 1997 Sep, 131(3), 398 - 404
Incidence of bacteremia in infants and children with fever and petechiae; Mandl KD et al.; OBJECTIVE: We determined the incidence of serious invasive bacteremia caused by Neisseria meningitidis and other organisms in febrile infants and children with a petechial rash . Further, we studied the diagnostic value of laboratory and clinical finding in these patients . STUDY DESIGN: We conducted this prospective cohort study in the emergency department of an urban pediatric teaching hospital, during an 18-month period, and enrolled consecutive patients with temperature of 38 degrees C or higher and petechiae . Our measures included (1) laboratory tests (leukocyte count, coagulation profile, blood culture, and cerebrospinal fluid bacterial culture); (2) a questionnaire requesting clinical data including general appearance, number and location of petechiae, and presence or absence of purpura; and (3) a follow-up telephone survey documenting health status . RESULTS: A total of 411 patients were enrolled, with 57.7% between 3 and 36 months of age . Eight patients (1.9%) had bacteremia or clinical sepsis . Six had serious invasive bacteremia: N . meningitidis (two patients), group A streptococcus (one), or sepsis with negative culture results (three) . Two had occult bacteremia caused by Streptococcus pneumoniae and no evidence of sepsis . No patient had a positive cerebrospinal fluid culture result . None of the 357 well-appearing patients (95% confidence interval: 0.0%, 1.0%) had serious invasive bacteremia . Fifty-three patients appeared ill, including all six with serious invasive bacteremia . Ill appearance of the child had a sensitivity of 1.00 (95% confidence interval: 0.60, 1.00), and a leukocyte count of 15,000 or greater, or of less than 5000, had a sensitivity of 1.0 (95% confidence interval: 0.53, 1.00) for detecting serious invasive bacteremia . All children with meningococcemia had purpura . CONCLUSIONS: Invasive bacteremia occurred less frequently in our study than in previous series and was identified by clinical criteria . Our data support the treatment of selected well-appearing children with fever and petechiae as outpatients.

Eur J Obstet Gynecol Reprod Biol, 1997 Aug, 74(2), 145 - 7
Endocervical infection in a pregnant woman caused by Neisseria meningitidis: evidence of associated oropharyngeal colonization of the male partner; Harriau P et al.; A case of premature birth associated with an endocervical infection caused by Neisseria meningitidis is reported . Treatment of the mother with amoxycillin eradicated the bacteria from the endocervix and avoided newborn colonization or infection . Epidemiological investigation identified meningococcal oropharyngeal colonization of the male partner . The two strains were of the same antigenic formula B:4:P1.14 and exhibited identical rDNA restriction fragment patterns and outer membrane protein profiles . This phenotypic and genomic identity of strains is the first clear evidence for cross-colonization between sexual partners.

Acta Paediatr, 1997 Sep, 86(9), 1009 - 10
Screening for complement deficiency in bacterial meningitis; Ernst T et al.; Seventy-seven children with bacterial meningitis were screened for complement deficiency . Both the classical and the alternate pathways were normal in 75 patients . Transiently reduced total haemolytic activity of the classical pathway was documented in a boy with meningococcal meningitis . Total haemolytic activity of both the classical and the alternate pathways were reduced in another patient with pneumococcal meningitis: individual complement components determination indicated predominant activation of the alternate pathway.

J Acquir Immune Defic Syndr Hum Retrovirol, 1997 Aug 15, 15(5), 375 - 80
HIV-1 risk and vaccine acceptability in the Ugandan military; Hom DL et al.; Between July and October 1993, 570 19- to 22-year-old volunteers were screened for HIV-1, with a resulting seroprevalence rate of 18.3% (95% CI: 14.0%, 22.6%) . A cohort of 249 HIV-1-noninfected military recruits in the Ugandan Peoples' Defense Forces was followed prospectively for up to 18 months to document rates of HIV-1 seroprevalence, seroconversion, and knowledge and attitudes related to vaccine acceptability . The HIV-1 seroincidence rate was 3.56 per 100 person-years (95% CI: 1.49, 5.62) over 309 person-years of observation . At the 3- and 12-month visits, subjects were interviewed on issues of acceptance and knowledge about vaccines, including anti-HIV vaccines in particular . More than 90% believe that HIV vaccines will not cause HIV infection, and if offered, 88% report that they would take the vaccine if they were not already infected . Nonvaccine prevention methods were considered less reliable; monogamy and condom use were considered effective by only 33.5% and 69.3% of the cohort respectively . After completing the vaccine acceptability questionnaire at the 12-month visit, subjects were offered an approved polyvalent meningococcal vaccine as an indicator of general vaccine acceptance . All subjects reported receiving at least one previous vaccination, and 95% willingly accepted the meningococcal vaccination . The Ugandan military is a stable population at substantial risk for HIV-1 infection and may be a suitable population for vaccine efficacy trials.

Rev Prat, 1997 Sep 1, 47(13), 1428 - 32
{Febrile purpura in children}; Gillet Y et al.; The association of fever and purpura should first suggest the diagnosis of fulminant meningococcemia, owing to the severity of this condition . Compromise of peripheral circulation (cyanosis, prolonged refilling time) is important to consider, because normal blood pressure is usually observed at an early stage of a septic shock in children and particularly in young infants . When this hypothesis has been eliminated, other causes of febrile purpura can be considered: meningococcal meningitis; measles or other viral diseases; non infectious causes include mechanical purpura, Schonlein-Henoch's purpura and thrombocytopenia . In the frequent case where no cause has been found, the diagnosis of occult bacteriaemia should be considered, leading to parenteral administration of antibiotic following blood and cerebrospinal fluid cultures.

Clin Microbiol Rev, 1997 Oct, 10(4), 650 - 73
A week in the life of a travel clinic; Blair DC; International travel has increased enormously in recent years . With the greater movement of people have come increased encounters with a wide variety of diseases: malaria, dengue, cholera, typhoid fever, Ebola virus, and many more . The need for greater scope, consistency, and knowledgeability in pretravel health care to meet these challenges has been met by the emergence of the discipline of travel medicine . Travelers are well advised to become informed of the risks they face and to take steps to minimize those risks . After reviewing a traveler's medical history and a detailed itinerary, a travel medicine practitioner can offer expert advice on behavioral modifications, immunizations, and chemoprophylaxis regimens which will increase the traveler's margin of safety . The issues most frequently addressed in a travel clinic include treatment of traveler's diarrhea, malaria chemoprophylaxis, and immunizations, for hepatitis A, typhoid fever, tetanus/diphtheria, influenza, pneumococcus, hepatitis B, polio, meningococcus, measles, mumps, rubella, varicella, and rabies . Pretravel consultation must consider the age and underlying health problems of the traveler, the nature of the trip (wilderness, jungle, rural, urban, resort, or cruise), the duration of travel, and the latest available information on the site in terms of disease outbreaks, terrorism, and natural calamities.

J Bacteriol, 1997 Oct, 179(20), 6400 - 7
Identification of human transferrin-binding sites within meningococcal transferrin-binding protein B; Renauld-Mongenie G et al.; Transferrin-binding protein B (TbpB) from Neisseria meningitidis binds human transferrin (hTf) at the surface of the bacterial cell as part of the iron uptake process . To identify hTf binding sites within the meningococcal TbpB, defined regions of the molecule were produced in Escherichia coli by a translational fusion expression system and the ability of the recombinant proteins (rTbpB) to bind peroxidase-conjugated hTf was characterized by Western blot and dot blot assays . Both the N-terminal domain (amino acids {aa} 2 to 351) and the C-terminal domain (aa 352 to 691) were able to bind hTf, and by a peptide spot synthesis approach, two and five hTf binding sites were identified in the N- and C-terminal domains, respectively . The hTf binding activity of three rTbpB deletion variants constructed within the central region (aa 346 to 543) highlighted the importance of a specific peptide (aa 377 to 394) in the ligand interaction . Taken together, the results indicated that the N- and C-terminal domains bound hTf approximately 10 and 1000 times less, respectively, than the full-length rTbpB (aa 2 to 691), while the central region (aa 346 to 543) had a binding avidity in the same order of magnitude as the C-terminal domain . In contrast with the hTf binding in the N-terminal domain, which was mediated by conformational epitopes, linear determinants seemed to be involved in the hTf binding in the C-terminal domain . The host specificity for transferrin appeared to be mediated by the N-terminal domain of the meningococcal rTbpB rather than the C-terminal domain, since we report that murine Tf binds to the C-terminal domain . Antisera raised to both N- and C-terminal domains were bactericidal for the parent strain, indicating that both domains are accessible at the bacterial surface . We have thus identified hTf binding sites within each domain of the TbpB from N . meningitidis and propose that the N- and C-terminal domains together contribute to the efficient binding of TbpB to hTf with their respective affinities and specificities for determinants of their ligand.

FEMS Immunol Med Microbiol, 1997 Sep, 19(1), 1 - 5
Reactivity of the new monoclonal antibody '22' with meningococcal strains isolated from patients and carriers in Greece; Tzanakaki G et al.; Previous studies found that the majority of Neisseria meningitidis isolates from either patients or carriers in Greece do not react with the monoclonal antibodies used at present in the whole-cell ELISA (WCE) for determination of serotype and subtype antigens . A new monoclonal antibody designated '22' produced by the National Meningococcal Reference Laboratory in the Czech Republic was assessed in the whole-cell ELISA with 257 non-typable meningococcal strains from both patients (52) and carriers (205) . The carrier strains included 34 non-typable isolates from two immigrant populations: ethnic Greeks who have immigrated from Russia since 1989 (19/75) and Kurdish refugees (15/34) . Approximately 10% of the meningococcal strains isolated from patients and 11.7% of the carrier strains reacted with the reagent . Although the majority of meningococcal isolates from resident Greeks were not typable with the antibody, 11/19 (57.9%) of the carrier strains from Russian immigrants and 4/15 (20%) of those from the Kurdish refugees reacted with the new reagent.

Infect Immun, 1997 Oct, 65(10), 4341 - 9
Attachment of piliated, Opa- and Opc- gonococci and meningococci to epithelial cells elicits cortical actin rearrangements and clustering of tyrosine-phosphorylated proteins; Merz AJ et al.; Attachment of piliated Neisseria gonorrhoeae or Neisseria meningitidis cells to A431, Chang, HEC-1-B, or polarized T(84) cells triggers rearrangements of cortical microfilaments and the accumulation of phosphotyrosine-containing proteins at sites of bacterial contact . Actin stress fibers and the microtubule network remain unaltered in infected cells . The rearrangements reported here are triggered by piliated, Opa- and Opc- strains and also by nonpiliated gonococci (GC) that produce the invasion-associated OpaA protein . Thus, neisserial adhesion via either of at least two different adhesins can trigger cortical rearrangements . In contrast, these rearrangements are not triggered by nonadherent GC or meningococcal strains, by heat-killed or chloramphenicol-treated GC strains, or by Escherichia coli recombinants that adhere to cells via GC OpaA or Opal fusion proteins, suggesting that additional neisserial components are involved . Immunoblotting experiments did not detect consistent increases in the phosphorylation of specific proteins . Possible biological implications of these Neisseria-induced cortical rearrangements are discussed.

Infect Immun, 1997 Oct, 65(10), 4022 - 9
Complement factor C3 deposition and serum resistance in isogenic capsule and lipooligosaccharide sialic acid mutants of serogroup B Neisseria meningitidis; Vogel U et al.; Serogroup B meningococci express sialic acids on their surfaces as a modification of the lipooligosaccharide (LOS) and as capsular material consisting of alpha2,8-linked sialic acid homopolymers . The aim of this study was to elucidate the impact of each sialic acid component on the deposition of complement factor C3 and serum resistance . For this purpose, we used isogenic mutants deficient in capsule expression (a polysialyltransferase mutant) or sialylation of the LOS (a galE mutant) or both (a mutant with a deletion of the cps gene locus) . Bactericidal assays using 40% normal human serum (NHS) demonstrated that both the capsule and LOS sialic acid are indispensable for serum resistance . By immunoblotting with monoclonal antibody MAb755 that is specific for the C3 alpha-chain, we were able to demonstrate that C3 from 40% NHS was covalently linked to the surface structures of meningococci as C3b and iC3b, irrespective of the surface sialic acid compounds . However, C3b linkage was more pronounced and occurred on a larger number of target molecules in galE mutants with nonsialylated LOS than in meningococci with wild-type LOS, irrespective of the capsule phenotype . C3b deposition was caused by both the classical pathway (CP) and the alternative pathway of complement activation . Use of 10% NHS revealed that at low serum concentrations, C3 deposition occurred via the CP and was detected primarily on nonsialylated-LOS galE mutants, irrespective of the capsular phenotype . Accordingly, immunoglobulin M (IgM) binding to meningococci from heat-inactivated NHS was demonstrated only in both encapsulated and unencapsulated galE mutants . In contrast, inhibition of IgA binding required both encapsulation and LOS sialylation . We conclude that serum resistance in wild-type serogroup B meningococci can only be partly explained by an alteration of the C3b linkage pattern, which seems to depend primarily on the presence of wild-type LOS, since a serum-resistant phenotype also requires capsule expression.

FEBS Lett, 1997 Sep 8, 414(2), 409 - 13
Characterisation of the meningococcal transferrin binding protein complex by photon correlation spectroscopy; Boulton IC et al.; Photon correlation spectroscopy demonstrated for the first time that co-purified meningococcal TbpA+B form a complex in solution . This structure bound hTf and the resultant species underwent partial dissociation after exposure to additional hTf or following prolonged incubation . Purified TbpA and TbpB had similar apparent sizes but showed distinctive size profiles suggesting that TbpA forms a largely homogeneous population while TbpB may produce more variable particle sizes under these conditions.

Clin Infect Dis, 1997 Sep, 25(3), 640 - 6
Meningococcal septic shock in children: clinical and laboratory features, outcome, and development of a prognostic score; Kornelisse RF et al.; The clinical characteristics of and outcome for 75 children with meningococcal septic shock were studied . In addition, a new prognostic scoring system was developed . The median age of the patients was 3.2 years (range, 3 weeks to 17.9 years) . The most common phenotype of Neisseria meningitidis was B:4:P1.4 (27%) . A mortality rate of 21% was observed . Ten (17%) of the 59 survivors had serious sequelae . Calcium levels were significantly lower in patients with seizures . Disseminated intravascular coagulation occurred in 58% of the patients who were tested . Logistic regression analysis identified four laboratory features independently associated with mortality: serum C-reactive protein level, base excess, serum potassium level, and platelet count . These features were used to develop a novel scoring system with a predictive value for death and survival of 71% and 90%, respectively . The outcome was predicted correctly for 86% of the patients, which is higher than rates previously reported for scoring systems.

Lancet, 1997 Sep 20, 350(9081), 880 - 2
"Love's labours lost": failure to implement mass vaccination against group A meningococcal meningitis in sub-Saharan Africa; Robbins JB et al.; PIP: Despite the availability of a safe, effective polysaccharide vaccine, group A meningococcal meningitis epidemics persist in sub-Saharan Africa . In October 1996, there were almost 150,000 reported cases and 15,000 deaths, the majority of which involved children . At 3 months of age, induction of protective group A meningococcal antibody levels requires 2 injections at least 1 month apart . Reinjection of 5-year-old children increases group A antibodies to long-term protective levels . During meningitis epidemics in Nigeria, Mali, and Rwanda, fatality was significantly reduced in areas where scarce vaccine was administered selectively . Although effective on an individual basis, selective vaccination is unable to control meningitis epidemics . In Chad, mass vaccination of the entire population (excluding infants under 12 months) eliminated the disease . Successful mass vaccination against group A meningococcal epidemics also has been reported in Saudi Arabia, China, and refugee camps in Africa . Although cost is cited as an obstacle to routine mass vaccination to prevent meningococcal meningitis in South Africa, prevention is the least expensive approach to disease control . It is recommended that the entire population of Africa's meningitis belt receive group A meningococcal vaccine in accordance with the recommended age schedule in a mass vaccination program .

Pathol Biol (Paris), 1997 Apr, 45(4), 274 - 80
Neisseria meningitidis: fifteen cases of bronchopulmonary infections associated with septicaemia; Angelini S et al.; From 1989 to 1995, 4,053 meningococcal strains with a clinical information form were sent to the National Reference Center for Meningococci (NRCM) . Among these strains 569 meningococci (14.04%) were isolated from secretions of the bronchopulmonary tract by expectoration or fibroscopy protected or not from contamination by microflora . Fifteen observations associated an infection of bronchopulmonary syndrome and a meningococcemia without any other symptoms . These patients were in general elderly (mean = 71.3 years old) except for two cases: one of them presented sickle cell anemia and the other was very young (13 months) . In all cases, there were signs of clinical and X-ray pneumopathies . Among the fifteen cases described, eight cases occurred during the winter, and four during the spring . Twelve were described in countries north of the Loire . Serogroup Y was isolated six times, serogroup B four times and serogroup C three times . The small quantity of cases did not permit us to study the distribution of serotype and serosubtype . Three patients, aged 92, 86 and 74 years old, died from the meningococcal infection.

Proteins, 1997 Sep, 29(1), 113 - 25
Bactericidal antibody recognition of a PorA epitope of Neisseria meningitidis: crystal structure of a Fab fragment in complex with a fluorescein-conjugated peptide; van den Elsen JM et al.; Class 1 outer membrane protein PorA of Neisseria meningitidis is a vaccine candidate against bacterial meningitis . Antibodies against PorA are able to induce complement-mediated bacterial killing and thereby play an important role in protection against meningococcal disease . Bactericidal antibodies are all directed against variable regions VR1 and VR2 of the PorA sequence, corresponding to loops 1 and 4 of a two-dimensional topology model of the porin with eight extracellular loops . We have determined the crystal structure to 2.6 A resolution of the Fab fragment of bactericidal antibody MN12H2 against meningococcal PorA in complex with a linear fluorescein-conjugated peptide TKDTNNNL derived from the VR2 sequence of sero-subtype P1.7,16 (residues 180-187) from meningococcal strain H44/76 . The peptide folds deeply into the binding cavity of the Fab molecule in a type I beta-turn, with the minimal P1.16 epitope DTNNN virtually completely buried . The structure reveals H-bonds and van der Waals interactions with all minimal epitope residues and one essential salt bridge between Asp-182 of the peptide and His-31 of the MN12H2 light chain . The key components of the recognition of PorA epitope P1.16 by bactericidal antibody MN12H2 correspond well with available thermodynamic data from binding studies . Furthermore, they indicate the structural basis of an increased endemic incidence of infection by group B meningococci in England and Wales since 1981 associated with the occurrence of an Neisseria meningitidis escape mutant (strain-MC58) . The observed three-dimensional conformation of the peptide provides a rationale for the development of a synthetic peptide vaccine against meningococcal disease.

Microb Pathog, 1997 Sep, 23(3), 139 - 55
Lipopolysaccharide heterogeneity and escape mechanisms of Neisseria meningitidis: possible consequences for vaccine development; Rune Andersen S et al.; We wanted to compare the potential protective capacity of antibodies to meningococcal lipopolysaccharides (LPS) . The frequency of occurrence and degree of expression of the epitopes recognized by murine monoclonal antibodies (MAbs) to immunotypes L3,7,9 (9-2-L379) and L8 (2-1-L8) and to the LPS inner core (216-Lc and 217-Lc), were determined among 77 consecutive Norwegian meningococcal patient isolates from 1995 . The immunotype L3,7,9 was strongly expressed by 95% of the isolates, whereas L8 was weakly to moderately expressed by 9% . The inner core epitopes, were widely distributed among the serogroup B organisms, but were proved weakly expressed . The bactericidal activity of the four MAbs to various selected strains, was found to correlate positively with the quantity of the LPS epitopes recognized by these four MAbs in the bacteria . When tested in the serum bactericidal assay (SBA), often a few percent of the colonies of the inocula survived high concentrations of the MAbs . The results indicate that escape from the bactericidal action could be achieved through: (i) selection of variants not expressing the LPS-epitope of the actual MAb, (ii) a relative reduction in the density of the LPS-epitope achieved by dilution with another LPS structure or (iii) other factors, not yet understood . In conclusion, antibodies to the L3,7,9 epitope seem to be of importance for protection, whereas antibodies to the epitopes of the LPS inner core or immunotype L8, are not likely to offer protection alone . However, in order to prevent escape through alteration of the LPS pattern of the microbes, various LPS structures should probably be present in the OMV vaccine.

Commun Dis Intell, 1997 Aug 21, 21(17), 233 - 6
Meningococcal disease in Australia; looking at the past, thinking of the future; Patel M; In 1987 an unexpected change in the epidemiology of meningococcal disease began in Australia . The change was accompanied by an outbreak of serogroup A meningococcal disease among Aboriginal central Australians, and was followed by a progressive rise in notifications of disease caused by both serogroup B and C nationwide . Over the last 4 years, the notification rate has plateaued at 2.1-2.3 per 100,000 population . Virulent clonal groups of serogroup A and C meningococci that have caused outbreaks appear to be identical to strains that have caused large outbreaks in other countries . We cannot predict where and when the next outbreak will occur . However, we can plan to respond swiftly when it does . This report presents an overview of the observed trends, the association between the microbiology and epidemiology of meningococcal disease, and the relevance of this association to outbreaks, with recommendations for management.

FEBS Lett, 1997 Aug 18, 413(2), 364 - 70
Identification of potential ferric binding residues in the iron-binding protein of pathogenic Neisseria meningitidis through structure-based multiple sequence alignments; Gorinsky B et al.; The ferric iron-binding proteins of pathogenic Neisseria display structural and metal-binding properties characteristic of the transferrin family . In the absence of structural data for the ferric iron-binding proteins, spacial folding templates have been derived for the meningococcal protein from complete and partial structure-based multiple sequence alignments with structurally related proteins . The templates have been used to identify a number of potential iron-binding residues . These include four residues that are identical with the iron coordinating ligands of transferrin, but only two reside within equivalent structural elements.
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vedi: Bibliografia sui danni neurologici (meningite ed altro) da Vaccino