MMWR Morb Mortal Wkly Rep, 2001 Mar 30, 50(12), 221 - 2 Update: assessment of risk for meningococcal disease associated with the Hajj 2001; Presenting features of meningococcal disease et al.; University of AucklandAIMS: To investigate whether the presenting features of meningococcal disease as promoted in public health awareness material and in the print media accurately reflect the clinical features in patients admitted to Auckland hospitals with meningococcal disease January 1998 to June 1999 . METHODS: Hospital record, public health message and newspaper article review, with analysis by presenting feature, age group and disease complex . RESULTS: The most common presenting features were fever (95%), rash (65%), vomiting and nausea (64%), lethargy (62%), headache (44%), refusing food and drink (35%), irritability (33%), muscle ache and joint pains (27%) and stiff neck (26%) . Public health messages gave appropriate emphasis to the key features, whereas newspaper articles under-emphasised these . The term 'meningitis' was used more frequently in newspapers (65%) than in public health messages (30%), despite meningitis alone presenting less frequently (38% of cases) than meningococcal septicaemia, and having a less serious prognosis . CONCLUSIONS: Presenting features currently noted in the Ministry of Health's health education resource material are appropriate . Public health specialists dealing with the media should ensure that appropriate messages are incorporated into media reports . A greater use of the term 'meningococcal disease' by both public health agencies and media would convey to the public the message that this disease has a spectrum of presenting features, with those of septicaemia more common, but also indicating an even greater need for urgency of action than with 'classical' meningitic features. Rev Med Liege, 2001 Feb, 56(2), 124 - 5 {Pharmacy clinics . Medication of the month . Meningitec}; Lepage P; Meningitec (Wyeth Lederle) is a new antimeningococcal C conjugate vaccine . This vaccine contains a group C meningococcal oligosaccharide coupled to a carrier protein (CRM197, a non toxic variant of diphteria toxoid) . This vaccine has been shown to be immunogenic both in adults and young children . Meningitec is well tolerated and its efficacy has been recently demonstrated in England (vaccine efficacy: 97% among adolescents; 92% among toddlers). Infect Immun, 2001 May, 69(5), 3203 - 13 Functional opsonic activity of human serum antibodies to inner core lipopolysaccharide (galE) of serogroup B meningococci measured by flow cytometry; Plested JS et al.; A recently described flow cytometric opsonophagocytic assay (OPA) was adapted to quantify the functional activity of serum antibodies specifically directed against serogroup B inner core lipopolysaccharide (LPS) of Neisseria meningitidis . The percentage of human peripheral polymorphonuclear leukocytes and monocytes (PMNms) ingesting fluorescently labeled, ethanol-fixed N . meningitidis organisms (phagocytic activity) in the presence of human sera was measured to reflect the serum opsonic activity against the bacterium . The contribution to opsonophagocytic activity of antibodies to inner core LPS was estimated by comparing the opsonic activities of adult and infant sera before and after adsorbing anti-LPS antibodies from the sera using purified LPS extracted from an LPS mutant (galE) of N . meningitidis strain MC58 (B:15:P1.7,16:L3) . The specificity of the assay was further investigated using monoclonal antibody (MAb) B5, which binds to an inner core LPS epitope of N . meningitidis . A dose-dependent decrease in phagocytic activity was observed when MAb B5 was incubated with LPS from an inner core LPS (galE) mutant . Similarly, the number of PMNms ingesting fluorescently labeled polystyrene beads coated with inner core (galE) LPS decreased in a dose-dependent fashion when MAb B5 was incubated with various concentrations of the homologous inner core LPS . Strong correlations were found between the concentration of serum antibodies to inner core LPS (galE) versus the phagocytic activity using healthy adult sera (r(2) = 0.89) . There was a correlation between phagocytic ingestion and initiation of intracellular oxidative burst (r(2) = 0.99) using polystyrene beads coated with inner core LPS and opsonized with the same sera using the oxidative burst indicator system dihydrorhodamine123/rhodamine 123 . OPA results were also found to correlate closely with the results of the serum bactericidal assay using MAb B5 against the N . meningitidis MC58 galE mutant in the presence of human complement (r(2) = 0.994, P = 0.003, two-tailed test) . These studies demonstrate that functional antibodies are produced in humans against meningococcal inner core LPS and that the OPA is a useful approach to study the opsonic activity of antibodies to inner core LPS in health and disease. Braz J Infect Dis, 2001 Feb, 5(1), 37 - 9 Two family members with a syndrome of headache and rash caused by human parvovirus B19; Pereira AC et al.; Human parvovirus B19 infection can cause erythema infectiosum (EI) and several other clinical presentations . Central nervous system (CNS) involvement is rare, and only a few reports of encephalitis and aseptic meningitis have been published . Here, we describe 2 cases of B19 infection in a family presenting different clinical features . A 30 year old female with a 7-day history of headache, malaise, myalgias, joint pains, and rash was seen . Physical examination revealed a maculopapular rash on the patient's body, and arthritis of the hands . She completely recovered in 1 week . Two days before, her 6 year old son had been admitted to a clinic with a 1-day history of fever, headache, abdominal pain and vomiting . On admission, he was alert, and physical examination revealed neck stiffness, Kerning and Brudzinski signs, and a petechial rash on his trunk and extremities . Cerebrospinal fluid analysis was normal . He completely recovered in 5 days . Acute and convalescent sera of both patients were positive for specific IgM antibody to B19 . Human parvovirus B19 should be considered in the differential diagnosis of aseptic meningitis, particularly during outbreaks of erythema infectiosum . The disease may mimic meningococcemia and bacterial meningitis. Trends Microbiol, 2001 Apr, 9(4), 181 - 5 Exploring the evolution of diversity in pathogen populations; Gupta S et al.; Pathogen biodiversity is an under-exploited source of inference regarding disease processes and the evolution of pathogens and pathogenesis . In addition, the structure of pathogen populations, especially for diverse organisms such as the meningococcus, has implications for public health interventions including vaccination and antibiotic use . The predominant paradigm for interpreting bacterial diversity has been the clonal population structure, which has been modified by the incorporation of the effects of horizontal genetic exchange . Multilocus models of variable antigens, which explore the effects of immune selection, provide alternative explanations for structured diversity in pathogen populations. Br J Biomed Sci, 2001, 58(1), 17 - 9 Meningococcal disease due to serogroup Y in Scotland, 1992-1999; Clarke SC et al.; Meningococcal disease is an important cause of morbidity and mortality . A retrospective analysis was performed of all cases of invasive group-Y disease that were laboratory-confirmed in Scotland between 1992 and 1999 . A total of 1881 meningococcal isolates were characterised, 78 of which were serogroup Y . The incidence of non-invasive group-Y disease remained level between 1992 and 1999 . Only 12 isolates were from invasive disease, comprising five strain types . Invasive group-Y disease was associated mostly with the young or old . Serogroup-Y meningococcal disease was uncommon and a rare cause of invasive disease in Scotland between 1992 and 1999; however, it is essential that microbiologists are aware of its potential for increasing in incidence due to the recent introduction of the MenC vaccine, and its increased incidence in the USA. J Clin Microbiol, 2001 Apr, 39(4), 1622 - 5 Random amplified polymorphic DNA assay as a rapid tool in screening for Neisseria meningitidis serogroup C isolates of electrophoretic type 24; Schmink S et al.; Neisseria meningitidis serogroup C (NMSC) isolates of electrophoretic type 24 (ET-24), as identified by multilocus enzyme electrophoresis, are the main cause of serogroup C meningococcal disease outbreaks and sporadic meningococcal disease in the United States . We evaluated a random amplified polymorphic DNA assay as a rapid tool to screen for isolates of ET-24 by testing 199 NMSC isolates of 51 different ETs . A sensitivity of 88% and a specificity of 87% was achieved in identification of ET-24 isolates when the patterns obtained by two primers, P1 and P5, were analyzed together. J Clin Microbiol, 2001 Apr, 39(4), 1235 - 40 Phenotypic and genotypic approaches to characterization of isolates of Neisseria meningitidis from patients and their close family contacts; Tzanakaki G et al.; Characterization of isolates of Neisseria meningitidis obtained from patients with meningococcal disease or from pharyngeal swabs of asymptomatic carriers can be achieved by several approaches which provide different levels of discrimination . A total of 45 gram negative, oxidase-positive diplococcus strains isolated from 15 individuals with meningococcal disease and 30 of their family contacts were examined by three approaches: serological typing, multilocus enzyme electrophoresis (MLEE), and multilocus sequence typing (MLST) . For 10 of the 15 patient and contact groups, all of the isolates were confirmed as meningococci, and the bacteria obtained from the patients and contacts, including their mother or principal caregiver in the case of children, were indistinguishable by all three methods . In the remaining five groups the isolates from the patients were distinct from those recovered from the contacts, and in three examples, in two separate groups, the contacts were shown by MLST to be carrying strains of Neisseria lactamica . The data obtained from the three techniques were consistent, although complete serological typing was possible for only a minority of isolates . Both MLEE and MLST established the genetic relationships of the isolates and identified members of known hypervirulent lineages, but MLST was faster than MLEE and had the additional advantages that it could be performed on noninfective material distributed by mail and that the results from different laboratories could be compared via the internet . Commun Dis Public Health, 2000 Dec, 3(4), 298 - 9 Effectiveness of the meningococcal vaccination programme for British Armed Forces recruits; Bergman BP et al.; After several clusters of meningococcal disease arose among recruits to the British Armed Forces, vaccination against A + C meningococcal disease was introduced for military recruits in 1992 . From 1993 onwards, no further clusters of group C infection were reported and incidence of meningococcal disease among trained soldiers fell, but there was no significant reduction in the overall incidence of meningococcal disease in recruits. Commun Dis Public Health, 2000 Dec, 3(4), 271 - 3 Survey of the prescribing of chemoprophylaxis to index cases of invasive meningococcal disease; Heywood P et al.; Chemoprophylaxis is given to contacts of cases of invasive meningococcal disease to reduce the risk of secondary cases by eradicating carriage . In the United Kingdom index cases are also recommended to receive chemoprophylaxis . This is usually undertaken by the clinical team managing the case . One hundred and fifty cases of probable meningococcal infection notified to the consultants in communicable disease control in a local health authority were reviewed to identify the proportion receiving chemoprophylaxis and to examine the final clinical outcome, in terms of diagnosis, of each case . Twenty-five per cent of notified cases (37) did not receive chemoprophylaxis and this proportion varied significantly between three local hospitals . We estimate that 15 of the 37 index cases who did not receive chemoprophylaxis were likely to have had invasive meningococcal disease. Commun Dis Public Health, 2000 Dec, 3(4), 267 - 70 Media management of a community outbreak of meningococcal meningitis; Singleton CD et al.; Cases and, particularly, clusters of meningococcal meningitis often create high levels of public concern and attract the interest of news media . We describe below our experience of managing intense local and national media interest during a community outbreak of meningococcal disease in Derbyshire . Our learning is set out as ten key recommendations . Four of these are around managing the media, including using a proactive press release, providing detailed briefings, using a single spokesperson and coordination of the response by a press officer experienced in media management . Another four describe how to deliver an appropriate on-site response, often requested during community intervention programmes . The two final recommendations relate to ensuring good communication and supporting staff during what is an intensely stressful period . We hope our experiences may help others if faced with a similar problem. Biotechnol Appl Biochem, 2001 Apr, 33(Pt 2), 91 - 8 Solution stability studies of the subunit components of meningococcal C oligosaccharide-CRM197 conjugate vaccines; Ho MM et al.; Spectroscopic methods were used to detect modifications in the structures of CRM197, the mutant diphtheria toxin, and meningococcal C capsular oligosaccharide following their conjugation and incubation at various temperatures . Meningococcal C oligosaccharide-CRM197 conjugate vaccines obtained from two different manufacturers were incubated at -20, 4, 23, 37 or 55 degrees C for 5 weeks or subjected to ten cycles of freeze-thawing . The CRM197 carrier protein and the saccharide components of the treated vaccines were monitored by CD and NMR spectroscopic techniques . CD data indicated incubation temperature-dependent conformational changes in the carrier protein from vaccine A . Modifications appeared in both secondary and tertiary structures of the conjugated CRM(197) when incubated at 23 degrees C or above . This was characteristic of the 'open' conformation previously observed for this protein component . The NMR spectra also indicated modification of the structure of the conjugated CRM197 component of vaccine A when incubated at 23 degrees C or above, but failed to show any modification in the conjugated oligosaccharide . On the other hand, the structure of the oligosaccharide chains in vaccine B appeared to be degraded following incubation at 55 degrees C, even though the thermal effect on the conjugated CRM197 was less apparent . Repeated freeze-thawing did not affect the CD or NMR spectra . In conclusion, the two meningococcal C oligosaccharide-CRM197 conjugate vaccines were stable when stored at their recommended temperatures, but were differently affected by elevated temperatures . The conjugates differ in their conjugation chemistry, attachment positions, oligosaccharide chain length and loading, as well as recommended pH and storage buffer, and their different stability properties can probably be attributed to a combination of these factors. J Bacteriol, 2001 Apr, 183(8), 2570 - 5 Genetic isolation of meningococci of the electrophoretic type 37 complex; Claus H et al.; Neisseria meningitidis (the meningococcus) is a naturally competent bacterial species in which intra- and interspecific horizontal gene transfer is a major source of genetic diversity . In strains of the electrophoretic type 37 (ET-37) complex and of the A4 cluster, we identified genomic DNA coding for a novel restriction-modification system and for the tail of a previously unidentified prophage . Furthermore, a novel 7.2-kb DNA segment restricted to clones of the ET-37 complex and the A4 cluster was isolated and shown to occur both as a plasmid (pJS-B) and as a chromosomal integration . Neither the genomic loci nor pJS-B was present in ET-5 complex, lineage 3, or serogroup A meningococci . The differential distribution of the DNA segments described herein, as well as of opcA, porB, nmeAI, nmeBI, and nmeDI described previously, supports the concept of genetic isolation of hypervirulent lineages responsible for most cases of serogroup C disease worldwide. Microb Pathog, 2001 Mar, 30(3), 139 - 48 Murine monoclonal antibodies to PorA of Neisseria meningitidis show reduced protective activity in vivo against B:15:P1.7,16 subtype variants in an infant rat infection model; Toropainen M et al.; The major outer membrane protein PorA of Neisseria meningitidis is the target for bactericidal serosubtyping antibodies and is currently considered as a potential vaccine candidate against group B meningococcal disease . Although the minor antigenic variability of the PorA has been increasingly recognized and described, its implication for vaccine design remains unclear . In this study, the protective activity of murine monoclonal PorA specific antibodies against four isogenic meningococcal P1.7,16 target strains, the prototype P1.7,16a and three loop 4 point mutation variants (designated P1.7,16b to d) constructed from reference strain H44/76 (B:15:P1.7,16a), was evaluated in the infant rat infection model . All monoclonal antibodies had been obtained by immunization of mice with outer membrane protein preparations from meningococcal serosubtype P1.7,16 reference strain H44/76 . A challenge dose of 10(5)cfu/pup was given i.p . 1-2 h after the i.p . injection of 1:100 diluted antibodies, and the development of bacteremia was assessed by culturing blood samples taken 6 h after challenge . MN14C11.6, a reference monoclonal antibody for serosubtype P1.7 epitope located in predicted loop 1 (VR1) identical in all the variants, was equally protective against all loop 4 variants . The three P1.16 specific monoclonal antibodies tested (MN5C11G, MN12H2 and 62D12-8) all completely protected animals against the prototype P1.7,16a, variably against the P1.7,16b and P1.7,16c, but not against the P1.7,16d variant . Our findings therefore suggest that certain subtype variants may escape protection in vivo conferred by PorA specific antibodies . Gac Sanit, 2000 Nov-Dec, 14(6), 422 - 8 {Shared surveillance: meningococcal disease vs influenza}; Moreno-Civantos A et al.; OBJECTIVE: To analyse the association between the behavior of meningococcal disease and influenza, using for this purpose population statistics for Spain for the period of 1964 to 1997 . METHODS: Ecological study of the incidence of meningococcal disease and influenza in Spain from 1964 to 1997, inclusive . The study used weekly statistical data for these diseases supplied by the Compulsory Disease Reporting System (Enfermedades de Declaracion Obligatoria, EDO) . The deterministic component of the meningococcal disease and influenza series was studied by means of spectral analysis based on the Fast Fourier Transformation, and the non-deterministic component was studied using the ARIMA model . The Box-Jenkins method was used for pre-bleaching the series, and a cross-correlation was subsequently established between the residuals in order to detect the presence of any significant correlations between the meningococcal disease and influenza series . RESULTS: During the period from 1964 to 1997, the week that showed, on average, the greatest number of cases for the season was week 7 in the case of meningococcal disease and week 6 in the case of influenza . Spectral analysis of the meningococcal disease and influenza series clearly demonstrated the annual periodicity of both series, and periodicity of nearly 11 years for meningococcal disease and slightly over 10 years for influenza . When cross-correlation is established after prebleaching the series, positive correlations are obtained in the results of lags 0, 1, 2, and 3 . Introducing influenza as an exogenous variable in the multivariate model of meningococcal disease corroborates these results . There was a statistically significant relationship between the two processes during the same week and with a three-week lapse . CONCLUSIONS: By means of a methodology not previously applied to this subject, and by the use of prolonged time-span, country-comprehensive population statistics (which includes several epidemics waves), an association was shown to exist between meningococcal disease and influenza . This suggests the need for the surveillance of the two processes in an interrelated manner. Aten Primaria, 2000 Oct 31, 26(7), 439 - 45 {Research activity on pediatric vaccines in Spain: descriptive analysis of prospective studies published between 1990 and 1998}; Dal-Re Saavedra R et al.; OBJECTIVE: To describe the overall characteristics of prospective studies on vaccines in children, performed by Spanish investigators and published between 1990 and 1998 . METHODS: Through a bibliographic research on MEDLINE and EMBASE, 24 prospective studies, performed in Spain, published as original papers, and with objectives directly related to the administration of vaccines to children have been identified . These studies were grouped as: clinical trials (group A), studies performed on established vaccination programmes (group B), and those that could not be included in the above mentioned groups (group C) . RESULTS: 5, 9 and 10 studies belonged to groups A, B and C, respectively . More than 12,800 subjects participated in these studies, belonging to both normal population or specific risk groups . In 11 studies, the study population comprised newborns and infants . The vaccines under investigation were: hepatitis B (10 studies), DTPe/Pa (6), MMR (3), flu (2), Hib (1), hepatitis A (1), and meningococcus A and C (1) to address different objectives (in most of them, immunogenicity and/or reactogenicity) . Nine had external financial support; 21 were performed by hospital and/or primary care investigators, and 18 in the Vasque Coutry, Madrid or Valencia . 13 publications reported obtaining informed consent, and 8 on the approval of the study protocol by an independent committee . Ten studies were published by international journals . CONCLUSIONS: This study shows that most of the studies are conducted by clinicians, with vaccines targetted to newborns and infants, with no external financial support, in a small number of autonomous communities, and usually published in Spanish Journals . The submission of this type of studies to a research ethics committee is desirable, something done to a lesser extent than obtaining informed consent. Clin Infect Dis, 2001 Apr 1, 32(7), 1004 - 9 Epub 2001 Mar 15. Meningococcal disease among children who live in a large metropolitan area, 1981-1996; Wang VJ et al.; Neisseria meningitidis is an important cause of serious bacterial infections in children . We undertook a study to identify meningococcal infections of the blood, cerebrospinal fluid, or both of children in a defined geographic area to describe the burden of disease and the spectrum of illness . We reviewed the medical records of all children aged <18 years who had meningococcal infections at the 4 pediatric referral hospitals in Boston, Massachusetts, from 1981 through 1996 . We identified 231 patients with meningococcal disease; of these 231 patients, 194 (84%) had overt disease and 37 (16%) had unsuspected disease . Clinical manifestations included meningitis in 150 patients, hypotension in 26, and purpura in 17 . Sixteen patients (7%) died . Although meningococcal disease is devastating to a small number of children, we found that the burden of pediatric disease that it caused at the 4 pediatric referral centers in this geographic region was limited; that patients with overt meningococcal disease are most likely to have meningitis; and that individual practitioners are unlikely to encounter a patient with unsuspected meningococcal disease. MMWR Morb Mortal Wkly Rep, 2001 Feb 16, 50(6), 97 - 8 Risk for meningococcal disease associated with the Hajj 2001; Reverse vaccinology et al.; IRIS, Chiron S.p.A., Via Fiorentina, 1, 53100, Siena, Italy . rino-rappuoli@chiron.it The conventional approach to vaccine development requires cultivation of the pathogenic microorganism and its dissection using biochemical, immunological, and microbiological methods in order to identify the components important for immunity . This method, while successful in many cases, failed to provide a solution for many of those pathogens for which a vaccine is not yet available . Today, the possibility of using genomic information allows us to study vaccine development in silico, without the need of cultivating the pathogen . This approach, which we have named 'reverse vaccinology', reduces the time required for the identification of candidate vaccines and provides new solutions for those vaccines which have been difficult or impossible to develop . The potential of this new approach is illustrated by the use of reverse vaccinology for the development of a vaccine against serogroup B meningococcus . The application of reverse vaccinology to other fields, including viral vaccines is discussed. Infect Immun, 2001 Apr, 69(4), 2718 - 22 Differential gene expression during meningeal-meningococcal interaction: evidence for self-defense and early release of cytokines and chemokines; Wells DB et al.; Using microarray technology, we studied the early differential expression of 3,528 genes in human meningothelial cells in response to meningococcal challenge . Thirty-two genes were up-regulated, and four were down-regulated . Those up-regulated included the tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8 (but not IL-1beta) genes, suggesting that meningeal cells may be a local and early source of these cytokines . Also, a trend in up-regulation of anti-apoptotic genes and down-regulation of pro-apoptotic genes was observed . This is the first evidence that meningothelial cells may mount cytoprotective responses to pathogenic bacteria. Infect Immun, 2001 Apr, 69(4), 2502 - 11 Transcriptional regulation of divergent capsule biosynthesis and transport operon promoters in serogroup B Neisseria meningitidis; Tzeng YL et al.; The clinically important serogroups B, C, Y, and W-135 of Neisseria meningitidis produce sialic acid capsules that are critical in pathogenesis . In each of these serogroups, the capsule transport (ctrABCD) and capsule biosynthesis (synABCD) operons are divergently transcribed from putative promoters located in a 134-bp intergenic region (J . S . Swartley, J . H . Ahn, L . J . Liu, C . M . Kahler, and D . S . Stephens, J . Bacteriol . 178:4052-4059, 1996) . In this study we further assessed the role of the intergenic sequence in the transcriptional regulation of the sialic acid capsules of N . meningitidis . Insertional mutagenesis or deletions of the 134-bp sequence in the serogroup B meningococcal strain NMB resulted in a marked reduction or elimination of ctrABCD and synABCD transcription, with a concomitant loss of encapsulation . Chromosomal transcriptional lacZ-ermC reporter fusions of syn and ctr promoters were constructed through allelic exchange . Using these constructs, both operons were found to be constitutively transcribed in meningococci, the biosynthesis operon about fourfold higher than the transport operon . Both promoters showed increased activity during stationary-phase growth . In addition to the promoters, a 70-bp 5' untranslated region (UTR) upstream of synA was found to have a direct repeat and an inverted repeat that overlapped three putative integration host factor binding sites . Mutation of this 70-bp UTR and of the direct repeat upregulated both syn and ctr transcription . Regulation through the synA UTR was absent in a K1 Escherichia coli strain that produces identical capsular polysaccharide, implicating species-specific regulation . Meningococcal sialic acid capsule expression is initiated by divergent promoters in a 134-bp intergenic region, is repressed at the transcriptional level by the 5' UTR of synA, is increased during stationary-phase growth, and shows species-specific regulation . Transcriptional regulation is another important control point for sialic capsule expression in N . meningitidis. Wien Klin Wochenschr, 2001 Feb 15, 113(3-4), 107 - 12 Sepsis-associated purpura fulminans in adults; Gamper G et al.; Sepsis-associated purpura fulminans is defined as septicemia, shock, disseminated intravascular coagulation and circulatory failure leading to multiple organ dysfunction . 40-70% of patients with sepsis-associated purpura fulminans die . Early prognostic factors in adults have not been well delineated yet . Aim of our study was 1) to evaluate currently used scoring systems for meningococcal septicemia in the setting of sepsis-associated purpura fulminans and 2) to assess if other parameters are feasible as early prognostic factors . From 1.1 1994-31.12.1998 twelve patients (female: 7; mean age: 31 (21; 43) years) were studied . Six patients (50%) died within 2 hours and 7 days after admission despite standard intensive treatment . On admission non-survivors had a more pronounced degree of disseminated intravascular coagulation compared to survivors (platelet count 18000 (15000; 45000) G/l vs . 119.000 (111000; 152000) G/l, (p = 0.03); fibrinogen 67 (50; 108) mg/dl vs . 356 (234; 483) mg/dl, (p = 0.02); PTZ 28% (20%; 30%) vs . 44% (35%; 51%), (p = 0.05); aPTT 120 (120; 128) sec vs . 46 (44; 69) sec, (p = 0.001) . Severity of lactic acidosis was significantly higher in non-survivors than in survivors (pH 7.08 (6.92; 7.21) vs . pH 7.4 (7.25; 7.4), (p = 0.02); lactate 13.5 (11; 15) mval/l vs . 6.0 (4.4; 6) mval/l, (p = 0.02); data presented as median (25-75% interquartile range) . In our patients the Glasgow Meningococcal Septicemia Prognostic Score (GMSPS) and the Niklasson-Score failed to distinguish between survivors and non-survivors (GMSPS 7 (6; 11) vs 7.5 (7; 9) out of 15; predicted mortality according to Niklasson-Score 73% vs 88%) . There was no difference in the APACHE II Score (22 (18.5, 24) vs 22 (20.25, 26)) . The severity of disseminated intravascular coagulation assessed by routine laboratory parameters and the degree of lactic acidosis on admission were the strongest predictors of outcome in patients with sepsis-associated purpura fulminans . Scoring systems developed for patients with meningococcal septicemia are of limited value in the setting of sepsis-associated purpura fulminans. Am J Med Genet, 2001 Apr 1, 99(4), 325 - 7 High prevalence of complement C7 deficiency among healthy blood donors of Moroccan Jewish ancestry; Halle D et al.; The incidence of the specific component deficiencies in various ethnic groups is not known, although there appears to be an ethnic predilection for C6 and C8alpha-gamma deficiencies in blacks, whereas C7 and C8beta deficiencies are predominantly noted in Caucasians . Infectious diseases, particularly recurrent meningococcal infections, are observed more commonly with late component deficiencies . In the current study, we have simplified the PCR technique by using site-directed mutagenesis and designer primers in a cohort of Israeli Moroccan Jewish blood donors to ascertain allele frequency in this ethnic group, which, based on earlier studies, was considered to be at risk for C7 deficiency . The total mutant allele frequency in this ethnic cohort was 1.1% of a total of 365 healthy Israeli Moroccan Jews, including one homozygote . The identification of mutant alleles was efficient and inexpensive, and hence a large cohort was studied . The finding of complement deficiency identifies individuals at risk for Neisserial infections, which are known to be potentially life-threatening . Conversely, when a patient of Moroccan ancestry is diagnosed with a Neisserial infection, it is important to determine the complement status . Mol Microbiol, 2001 Mar, 39(5), 1345 - 55 Generation and characterization of a PhoP homologue mutant of Neisseria meningitidis; Johnson CR et al.; Two-component regulatory systems are important regulators of virulence genes in a number of bacteria . Genes encoding a two-component regulator system, with homology to the phoP/phoQ system in salmonella, were identified in the meningococcal genome . Allele replacement was used to generate a meningococcal knock-out mutant of the regulator component of this system, and its phenotype was examined . The mutant displayed many differences in protein profiles compared with wild type, consistent with it being a gene-regulatory mutation . Many of the growth characteristics of the mutant were similar to those of phoP mutants of salmonella: it was unable to grow at low concentrations of magnesium and was sensitive to defensins and other environmental stresses . Magnesium-regulated differences in protein expression were abrogated in the mutant, indicating that the meningococcal PhoP/PhoQ system may, as in salmonella, respond to changes in environmental magnesium levels . These results are consistent with the PhoP homologue playing a similar role in the meningococcus to PhoP in salmonella and suggest that it may similarly be involved in the regulation of virulence genes in response to environmental stimuli in the meningococcus . In support of this conclusion, we found the mutant grew was unable to grow in mouse serum and was attenuated in its ability to traverse through a layer of human epithelial cells . Identification of those genes regulated by the meningococcal PhoP may provide a route towards the identification of virulence genes in the meningococcus. Thromb Haemost, 2001 Feb, 85(2), 240 - 4 Tissue factor pathway inhibitor (TFPI) levels in the plasma and urine of children with meningococcal disease; Eling M et al.; Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of the TF-dependent coagulation system . In meningococcal disease, up-regulation of tissue factor expression on blood monocytes and possibly on endothelial cells has the potential to trigger the activation of the TF-dependent pathway of coagulation . Intravascular coagulation is considered to be a major pathogenic factor in meningococcal disease . We postulated that imbalance between TF expression and TFPI concentration might lead to uncontrolled coagulation in meningococcal disease . The aim of this study was to assess the levels of total TFPI in the plasma of patients with meningococcal disease and assess whether increased leaking of the TFPI was occurring . TFPI antigen levels and activity were measured in the plasma of 54 patients with meningococcal disease, and 13 healthy control children . TFPI antigen level were also determined in the urines of 14 of the 54 and 9 healthy control children . Plasma TFPI activity was reduced in the meningococcal diseased patients (mean of 0.503 +/- 0.341 U/ml; control, 1.010 +/- 0.199 U/ml: p <0.0001), as was the TFPI antigen levels (mean of 54.85 +/- 35.05 ng/ml; Control, 94.51 +/- 11.44 ng/ml; p <0.0001) . In contrast, TFPI antigen levels were increased in the urine of these patients when compared to the levels found in the urine of the healthy control children (mean of 12.96 +/- 5.392 ng/mmol creatinine; Control, 0.239 +/- 0.191 ng/mmol creatinine; p <0.035) . A lack of correlation between TFPI-activity and TFPI-antigen plasma levels was observed (r = 0.002, p = 0.85) . This data is consistent with the hypothesis that in meningococcal disease there is increased inactivation of plasma TFPI by the up regulation of tissue factor expression but in addition increased clearance of TFPI in urine is occurring. Rev Med Liege, 2000 Oct, 55(10), 915 - 20 {Meningococcemia, recrudescence, diagnosis and treatment}; Tomat AM et al.; Meningococcemia is a severe Gram negative septicemia whose mortality may be as high as 30% . It occurs more frequently in children but the proportion of teenagers is increasing in Belgium . During the past decade, a slow but sustained rise in the incidence of this illness has been noted, with a predominance of the serogroup B . We describe the symptoms, which often are poor in the early stage, the different therapies, most of them being still under investigation, and the chemoprophylaxis . Without being alarmist, the diagnosis must be considered in any child with cutaneous rash, even atypical and tachycardia. Bone Marrow Transplant, 2001 Jan, 27(1), 79 - 84 Tetravalent meningococcal polysaccharide vaccine is immunogenic in adult allogeneic BMT recipients; Parkkali T et al.; Forty-four adult BMT recipients transplanted from an HLA-identical sibling donor were randomized to receive meningococcal polysaccharide (Men PS) vaccine either 8 (early group; 22 patients) or 20 (late group; 22 patients) months after BMT . The geometric mean concentrations (GMC) of antibodies to serogroup A Neisseria meningitidis (Men A) and serogroup C Neisseria meningitidis (Men C), determined by an EIA method, decreased during the first 6 months after BMT but remained at a stable level thereafter . Before vaccination the GMCs of anti-Men A were 1.53 microg/ml and 1.61 microg/ml, but 1 month after vaccination they were significantly higher, 3.46 microg/ml and 6.39 microg/ml, in the early and late groups . The GMCs of anti-Men C increased from 0.37 microg/ml and 0.44 microg/ml before vaccination to 3.31 microg/ml and 4.62 microg/ml at 1 month after vaccination in the early and late groups, respectively . By 6 months after vaccination the GMCs of Men antibodies had decreased to levels of about 50% of those measured at 1 month after vaccination . Two-fold responses to Men A PS were seen in 52% and 74% and to Men C PS in 76% and 89% of the BMT recipients in the early and late groups, respectively . Chronic GVHD had no influence on the vaccination response . In the present study, Men PS vaccine induced good and equal antibody responses to Men A and Men C PSs in allogeneic BMT recipients regardless of timing after BMT . Vaccination against Neisseria meningitidis should be considered, especially in the event of travelling or military service > or = 8 months after BMT. J Epidemiol Community Health, 2001 Apr, 55(4), 283 - 7 Dramatic decline of serogroup C meningococcal disease incidence in Catalonia (Spain) 24 months after a mass vaccination programme of children and young people; Salleras L et al.; STUDY OBJECTIVES: The objective of this study was to evaluate the effectiveness of a mass vaccination programme carried out in Catalonia (Spain) in the last quarter of 1997 in response to an upsurge of serogroup C meningococcal disease (SCMD) . DESIGN: Vaccination coverage in the 18 month to 19 years age group was investigated by means of a specific vaccination register . Vaccination effectiveness was calculated using the prospective cohort method . Cases of SCMD were identified on the basis of compulsory reporting and microbiological notification by hospital laboratories . Vaccination histories were investigated in all cases . Unadjusted and age adjusted vaccination effectiveness referred to the time of vaccination and the corresponding 95% confidence intervals (CI) were estimated at 6, 12, 18 and 24 months of follow up . SETTING: All population aged 18 months to 19 years of Catalonia . MAIN RESULTS: A total of seven cases of SCMD were detected at six months of follow up (one in the vaccinated cohort), 12 cases at 12 months (one in the vaccinated cohort), 19 cases at 18 months (two in the vaccinated cohort) and 24 at 24 months (two in the vaccinated cohort) . The age adjusted effectiveness was 84% (95%CI 30, 97) at six months, 92% (95%CI 63, 98) at 12 months, 92% (95% CI 71, 98) at 18 months and 94% (95%CI 78, 98) at 24 months . In the target population, cases have been reduced by more than two thirds (68%) two years after the vaccination programme . In the total population the reduction was 43% . CONCLUSION: Vaccination effectiveness has been high in Catalonia, with a dramatic reduction in disease incidence in the vaccinated cohort accompanied by a relevant reduction in the overall population . Given that vaccination coverage was only 54.6%, it may be supposed that this vaccination effectiveness is attributable, in part, to the herd immunity conferred by the vaccine. J Infect Dis, 2001 Apr 1, 183(7), 1079 - 86 Epub 2001 Mar 08. Active immunization with a detoxified Escherichia coli J5 lipopolysaccharide group B meningococcal outer membrane protein complex vaccine protects animals from experimental sepsis; Cross AS et al.; The passive infusion of antibodies elicited in rabbits with a detoxified J5 lipopolysaccharide (LPS)/group B meningococcal outer membrane protein complex vaccine protected neutropenic rats from heterologous lethal gram-negative bacterial infection . In this study, active immunization was studied in neutropenic rats infected with Pseudomonas aeruginosa, in the presence or absence of ceftazidime therapy, and with Klebsiella pneumoniae . This vaccine elicited a > 200-fold increase in anti-J5 LPS antibody, which remained elevated throughout the duration of cyclophosphamide-induced neutropenia and for < or = 3 months . There was improved survival among immunized versus control animals: 48% (13/28) versus 7% (2/29) in Pseudomonas-challenged rats; 61% (11/18) versus 0% (0/10) in Pseudomonas- and ceftazidime-treated rats; and 64% (9/14) versus 13% (2/15) in Klebsiella-challenged rats (P < 0.01 for each comparison) . Immunized animals had lower levels of bacteria in organs and lower levels of circulating endotoxin at the onset of fever . In conclusion, active immunization with an anti-endotoxin vaccine improved survival after infection with > or = 2 heterologous, clinically relevant bacterial species in immunocompromised animals . Active immunization with this vaccine merits further investigation. Scand J Infect Dis, 2001, 33(1), 56 - 9 Acute cellulitis: an unusual manifestation of meningococcal disease; Porras MC et al.; We describe 2 patients who both developed cellulitis due to Neisseria meningitidis and review 8 other cases reported since 1966 . Female patients outnumbered male patients by 8 to 2, and there were 5 children and 5 adults . Four cases were caused by the serogroup C meningococcus, 2 cases by serogroup B and 2 others by serogroup Y (the nature of the meningococcal group was not available in 2 cases) . Diverse medical underlying conditions were present in 4 of the adult patients . The periorbital region (in all 5 children), limb (in 3 adults), neck (in 1 adult) and face and neck (in 1 adult) were the locations of the meningococcal cellulitis . In all 10 patients, a favorable clinical response to the antibiotic therapy was documented and no relapses occurred . These cases indicate that N . meningitidis should be considered as a causative agent of cellulitis in the appropriate clinical setting, particularly in children with signs of periorbital infection or adults with underlying diseases. Vaccine, 2001 Feb 28, 19(15-16), 2020 - 8 IL-12-mediated increases in protection elicited by pneumococcal and meningococcal conjugate vaccines; Buchanan RM et al.; Interleukin-12 (IL-12) may be a beneficial adjuvant for augmenting vaccine efficacy against encapsulated bacteria such as Streptococcus pneumoniae and Neisseria meningitidis since it can stimulate production of interferon-gamma (IFN-gamma) and secretion of antibody isotypes that are efficient at mediating complement fixation and opsonophagocytosis . In this study, we demonstrate the ability of IL-12 to enhance murine antibody responses, particularly IgG2a levels, to both pneumococcal and meningococcal conjugate vaccines . Transfer of immune serum from mice immunized with the meningococcal conjugate vaccine and IL-12 resulted in increased survival times, whereas transfer of serum from mice immunized with the pneumococcal conjugate and IL-12 resulted in protection from death upon bacterial challenge . Although treatment with vaccine and IL-12 increased levels of IFN-gamma mRNA, IL-12-mediated enhancement of antibody responses still occurred in IFN-gamma(-/-) mice . The results demonstrate the effectiveness of IL-12 as an adjuvant for polysaccharide conjugate vaccines, especially the pneumococcal conjugate vaccine. Vaccine, 2001 Feb 28, 19(15-16), 2006 - 11 Surveillance of infectious diseases in the Italian military as pre-requisite for tailored vaccination programme; D'Amelio R et al.; Surveillance and control of infectious diseases in the Italian military include prompt reporting of all occurring cases and prophylaxis through compulsory vaccination practices . The last mandatory immunisation programme in the Italian military was launched in 1998 (more than 10 years after the previous programme was introduced in 1986-1987) and it was planned according to the epidemiological data herein reported . The incidence rates (number of cases x 100000 subjects) of infectious diseases notified during the period 1976-1980 were compared with the corresponding figures notified 15 years later (1991-1995) . An increase of three airborne-transmitted viral diseases--varicella, rubella and measles--counterbalanced by a decrease of other infectious diseases, such as mumps, typhoid fever, tuberculosis, viral hepatitis, scabies, syphilis and gonorrhea, was observed . This may be related to improvements in the general hygienic conditions and more responsible sexual behaviour among Italian military recruits . Moreover, incidence rates of cases notified in the military were compared with those notified in the general population of the same sex- and similar age-range (15-24 years) over a 12-year period (1986-1997), to monitor the epidemiological situation in relation to (a) potential risk factors specifically linked to military life and (b) protective effects induced by specific vaccinations . Airborne-transmitted viral diseases, such as varicella, rubella, measles and mumps--which are usually underreported among civilians--show higher incidence rates in the military . Meningococcal meningitis shows higher incidence rates in the military in 1986 and 1987 (before the introduction of mandatory specific vaccination) as well as in 1995-1997 (main etiologic agent N . meningitidis serogroup B); similar rates were instead observed in the other years . Incidence rates for typhoid fever are generally lower in the military, despite the community life, probably reflecting the protective efficacy of specific vaccine . Hepatitis A and B show similar rates between military and civilian population . Finally, pulmonary tuberculosis generally shows higher rates in the military . These data therefore allow the conclusion that the only infectious diseases, for which possible risk factors in the military life may be hypothesised, seem to be meningococcal meningitis and perhaps pulmonary tuberculosis . Epidemiological surveillance of infectious diseases in the military as a pre-requisite for appropriate public health intervention strategy represents a good model to be followed also in larger contexts. Vaccine, 2001 Feb 28, 19(15-16), 1989 - 97 Development of a new method for the quantitative analysis of the extracellular polysaccharide of Neisseria meningitidis serogroup A by use of high-performance anion-exchange chromatography with pulsed-amperometric detection; Ricci S et al.; A new method for the quantitative determination of Neisseria meningitidis group A (MenA) capsular polysaccharide (CPS) has been developed . The method is based on trifluoracetic acid (TFA) hydrolysis of the CPS (2 M at 80 degrees C for 3 h), followed by chromatographic separation and quantification of the liberated mannosamine-6-phosphate from the area of the peak obtained using an IonPac AS11 column coupled to the sensitive pulsed amperometric detector ED40 . The highly selective nature of this method circumvents the interference problems associated with the classical method based on a colorimetric assay for phosphorus . Provided that suitable hydrolysis conditions can be found, this chromatographic approach might be applicable to the quantification of other bacterial antigens containing phosphorylated sugars such as meningococcal groups H, L, X and Z, and pneumococcal serotypes 6, 10A and 19. Pediatr Infect Dis J, 2001 Feb, 20(2), 153 - 9 Safety and immunogenicity of four doses of Neisseria meningitidis group C vaccine conjugated to CRM197 in United States infants; Rennels MB et al.; BACKGROUND: Following widespread use of conjugate pneumococcal vaccine, Neisseria meningitidis likely will become the leading cause of bacterial sepsis and meningitis in US children . This report describes the safety and immunogenicity in US children of four consecutive doses of a meningococcal group C vaccine conjugated to CRM197 via reductive amination (MnCC) . METHODS: One hundred six healthy 2-month-old infants received MnCC at 2, 4 and 6 months of age in a randomized, controlled double blind study; children in the other treatment arm were given a 7-valent conjugate pneumococcal vaccine . Parents reenrolled 64 of these children at 12 to 15 months to receive a fourth dose of MnCC . Routine childhood vaccines, including DTP, were coadministered . Temperatures and symptoms were recorded for 3 days after each immunization . Serum enzyme-linked immunosorbent assay IgG and bactericidal antibodies were measured prevaccination and before and 1 month after Doses 3 and 4 . RESULTS: Moderate to severe local reactions, defined as erythema or induration > or =2.4 cm or pain that interfered with limb movement was reported after 0 to 3.2% of MnCC injections, depending on the reaction and dose . Fever occurred in 23 to 37% of children, but the contribution of MnCC to the febrile reactions is unknown . Geometric mean concentrations of IgG antibody to group C meningococcal polysaccharide were 3.72 microg/ml after Dose 3 and 8.03 microg/ml after the booster . Geometric mean functional serum bactericidal antibody titers after Doses 3 and 4 were 1:463 and 1:2341, respectively . One hundred percent of children had a serum bactericidal antibody titer of > or =1:64 after three doses and > or = 1:128 after the booster . CONCLUSIONS: The MnCC vaccine had an acceptable safety profile and generated high titers of bactericidal antibody in immunized US infants and toddlers . It appears to be an attractive candidate vaccine for the prevention of serogroup C meningococcal disease in young children. J Antimicrob Chemother, 2001 Mar, 47(3), 285 - 96 Polymorphism of Neisseria meningitidis penA gene associated with reduced susceptibility to penicillin; Antignac A et al.; We studied polymorphism of penA (which encodes penicillin-binding protein 2) in 13 strains of Neisseria meningitidis susceptible to penicillin (pen(S)) and 12 strains with reduced susceptibility to penicillin (pen(I)) . These strains differed in geographical origin . Serological and genetic typing showed that they were highly diverse and belonged to several genetic lineages . Restriction analysis and DNA sequencing of penA showed that all pen(S) strains had the same penA allele regardless of genetic group, whereas pen(I) strains harboured various penA alleles . Transformation with amplicons of penA and genomic DNA from several pen(I) strains conferred the pen(I) phenotype on a pen(S) strain . Thus, reduction in susceptibility to penicillin is directly related to changes in penA and analysis of penA polymorphisms could be used as a reliable tool for characterizing meningococcal strains in terms of their susceptibility to penicillin. Rev Med Interne, 2001 Jan, 22(1), 75 - 8 {Primary Neisseria meningitidis arthritis of the knee without meningitis: contribution of synovial fluid culture in blood-culture vial}; Cartolano GL et al.; INTRODUCTION: Primary meningococcal arthritis is a rare form of meningococcal disease . It occurs as an isolated acute purulent arthritis without meningitis, and presence of Neisseria meningitidis in articular fluid . We report a new case of typical primary meningococcal arthritis . EXEGESIS: A previously healthy 23-year-old female patient was admitted for purpuric lesions of the legs . At admission, conscience was normal and symptoms of meningitis were absent . During the 2nd day of hospitalisation, a warm and painful effusion in the right knee appeared . Aspiration from the right knee yielded a purulent fluid . N . meningitidis was isolated from a blood-culture vial inoculated with the synovial fluid, while blood cultures remained sterile . Anti-biotherapy was initiated as soon as microbiological diagnosis was established . The patient was symptom-free 1 month later . CONCLUSION: We emphasize the fact that agar cultures of the synovial fluid remained sterile, while N . meningitidis grew in a blood-culture vial . We suggest that diagnosis of primary meningococcal arthritis may be underestimated when inappropriate culture media are used. Epidemiol Infect, 2000 Dec, 125(3), 555 - 60 Determinants of case fatality rates of meningococcal disease during outbreaks in Makkah, Saudi Arabia, 1987-97; El Bushra HE et al.; We studied case-fatality rates (CFRs) among cases of meningococcal disease (MCD) admitted to Makkah (Saudi Arabia) hospitals during the period 1988-97 . Of 483 cases, 431 (89.2%) were due to strains of serogroup A, 31 (6.4%) to serogroup W135, 16 (3.3%) to serogroup C, and 5 (10%) to serogroup B . Eighty-one patients died (case fatality rate (CFR)) 16.8%, 95% CI 13.5%, 20.4%) . The CFR in infections due to serogroup A strains was 14.8%, and for other serogroups it was 32.7% (95% CI 20.3%, 47.1%) . The CFR of MCD due to N . meningitidis serogroup A increased steadily with age (P<0.05) . Seeking first medical help at a foreign Hajj medical mission and being treated in a non-specialized hospital were associated with a higher case fatality rate. Bull World Health Organ, 2001, 79(1), 22 - 7 Epub 2003 Nov 05. The use of hospital-based nurses for the surveillance of potential disease outbreaks; Durrheim DN et al.; OBJECTIVE: To study a novel surveillance system introduced in Mpumalanga Province, a rural area in the north-east of South Africa, in an attempt to address deficiencies in the system of notification for infectious conditions that have the potential for causing outbreaks . METHODS: Hospital-based infection control nurses in all of Mpumalanga's 32 public and private hospitals were trained to recognize, report, and respond to nine clinical syndromes that require immediate action . Sustainability of the system was assured through a schedule of regular training and networking, and by providing feedback to the nurses . The system was evaluated by formal review of hospital records, evidence of the effective containment of a cholera outbreak, and assessment of the speed and appropriateness of responses to other syndromes . FINDINGS: Rapid detection, reporting and response to six imported cholera cases resulted in effective containment, with only 19 proven secondary cholera cases, during the two-year review period . No secondary cases followed detection and prompt response to 14 patients with meningococcal disease . By the end of the first year of implementation, all facilities were providing weekly zero-reports on the nine syndromes before the designated time . Formal hospital record review for cases of acute flaccid paralysis endorsed the value of the system . CONCLUSION: The primary goal of an outbreak surveillance system is to ensure timely recognition of syndromes requiring an immediate response . Infection control nurses in Mpumalanga hospitals have excelled in timely weekly zero-reporting, participation at monthly training and feedback sessions, detection of priority clinical syndromes, and prompt appropriate response . This review provides support for the role of hospital-based nurses as valuable sentinel surveillance agents providing timely data for action. Med Pregl, 2000 Jul-Aug, 53(7-8), 401 - 4 {Acute meningococcemia in a 4-month-old infant}; Topalovic R et al.; INTRODUCTION: What causes meningococcial diseases (MD) is a Gramm-negative diplococcus Neisseria meningitidis (meningococcus) . Most frequently it manifests itself in the form of meningitis and meningococcemia . The mortality rate of those suffering from MD has not significantly changed for three decades and ranges from 7% to 19%, and for meningococcemia from 18% to 53% . According to the data presented by domestic authors, of the total of the diseased with bacterial meningitis 75% are children with mortality rate from 6% to 15% . Severe forms of meningococcemia sometimes have extremely rapid development and lethal outcome within a few hours . Key elements for establishing the diagnosis of meningococcemia are presence of hemorrhagic rash with high fever, loss of interest in the environment, loss of consciousness and paleness . CASE REPORT: The boy was admitted to hospital as an emergency case on 29 December 1988 at 11:45 . The disease manifested abruptly the day before . He burst into tears easily, would take very little food and in the evening his temperature rose T degree 40.8 degrees C . Before midnight, in the village he was given injections of: lincomycin 300 mg and lasdol 250 i.m . During admittance the infant was agitated, kept moaning . His skin was pail gray with dot-like and spot-like hematoma which were more numerous and intense on the left ear, lower part of the body, scrotum and legs . The infant breathed heavily and fast (FR: 100/min) Cardiologist's finding showed: tahicardia over 200/min, buffled tones, gallop rhythm, pulsating neck veins and edema point to acute heart failure . Large fontanelles remained swollen even after lumbar puncture (LP) and extraction of 15 ml of clear cerebro-spinal fluid . Soon after admittance the boy stopped moaning but didn't cry when pricked and slipped deeper into coma . During the third hour of treatment generalized convulsions began which lasted approximately 10 minutes and stopped after i.v . administered diazepam . The boy remained in coma the second day in lethargy and with swollen fontanelles on the third day, so the first subdural puncture was then performed bilaterally . On that occasion only from the right side 8 ml of reddish liquid was obtained . Right after he was admitted we began permanent transfusion, which lasted 17 days . On the first day he received fresh blood transfusion . He was administered benzinpenicilline, chloramphenicol-succinate, lanatoside, human albumins, dexamethasone... . Blood oxygenation was carried out in the first few days of illness during the exhibited cardio-respiratory failure . DISCUSSION: Among risk factors, which contribute to occurrence of meningococcemia, is also artificial infant food . The reported boy was incorrectly fed with overdiluted cow milk . That and apparent hemostasis brake-down only worsened anemia and increased susceptibility to infections . Although LP was performed when the boy was admitted and the nutritious foundation was soaked with cerebro-spinal fluid, no bacteria were isolated or their presence confirmed in cerebro-spinal fluid colored after Gramm's method, because the child was given linkomycin the previous night . CONCLUSION: On the basis of clinical findings, hemorrhagic rush, convulsions, coma and acute heart failure as well as the laboratory findings it was concluded that it was a case of severe meningococcemia, meningitis and subdural effusion . Listed therapy and six subdural punctures led to full recovery of the patient . Further examination by a pediatrician and a psychologist eliminated the possibility of mental deficiency . The boy is now a good fifth grade elementary school pupil. Dev Biol (Basel), 2000, 103, 93 - 104 Characterization of saccharide-CRM197 conjugate vaccines; Hsieh CL; A seven-valent pneumococcal conjugate and a Group C Meningococcal conjugate are at the late stage of development . Clinical studies have demonstrated the efficacy and safety of these vaccines and licensure of these vaccines will be approved in the near future . Several new techniques have been proposed for characterizing polysaccharide-protein conjugates and their production intermediates . We are evaluating some of these new techniques, particularly NMR and MALLS, to determine whether or not they provide useful information for conjugate production . In the production of polysaccharide protein conjugates, the degree of saccharide activation, location of activation site, and the molecular weight of activated saccharides may typically be determined . In our evaluation, techniques such as NMR and MALLS may have a limited applicability for testing polysaccharides and activated saccharides. Dev Biol (Basel), 2000, 103, 259 - 64 Quantification of free polysaccharide in meningococcal polysaccharide-diphtheria toxoid conjugate vaccines; Lei QP et al.; A precipitation method using deoxycholate/HCI has been applied successfully to separate unconjugated free polysaccharide from carrier protein-bound material in meningococcal polysaccharide-diphtheria toxoid conjugate vaccines . The method effectively separated free and bound polysaccharide in conjugate vaccines prepared from Neisseria meningitidis serotypes A, C, W135 and Y . Free polysaccharide remained in the supernatant after deoxycholate treatment while protein-bound polysaccharide was fully precipitated . Testing by both colorimetric assay and high performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) has confirmed the selective loss of protein-bound polysaccharide in samples of conjugate vaccine or conjugate vaccine mixed with known amounts of free polysaccharide . This rapid separation method requires minimum sample handling and is specific, reproducible, and allows assessment of free polysaccharide levels in vaccines at final container concentration. Dev Biol (Basel), 2000, 103, 251 - 8 Capillary electrophoretic analysis of meningococcal polysaccharide-diphtheria toxoid conjugate vaccines; Lamb DH et al.; Protein-polysaccharide conjugate vaccines are large, complex molecules that present challenges in terms of characterization . Free solution capillary electrophoresis using alkaline (pH 9-10) borate or glycine/NaOH buffers permitted electrophoresis of diphtheria toxoid (Dt) or meningococcal polysaccharide-Dt conjugates as well-formed, relatively broad peaks . Resolution was observed between the conjugate and the Dt peaks for some serotypes; however, overlap between Dt and one or more conjugate peaks was observed with both buffers . Inclusion of SDS in the separation buffer at a level above the critical micelle concentration allowed separation of Dt and Dt-conjugates of meningococcal serotypes A, C, Y and W135 . Using borate/SDS, a linear relationship between peak area and Dt concentration was observed between approximately 2 mg/ml and 20 microg/ml . A linear relationship between Dt peak area and injection times from 10 to 50 seconds was also observed . Capillary electrophoresis may therefore be a useful method for quantifying free protein level in meningococcal-Dt conjugate vaccines. Dev Biol (Basel), 2000, 103, 151 - 60 Structure activity studies on group C meningococcal polysaccharide-protein conjugate vaccines: effect of O-acetylation on the nature of the protective epitope; Michon F et al.; A series of group C meningococcal polysaccharide-tetanus toxoid (GCMP-TT) conjugates were prepared as vaccines with varying percentages of O-acetylation at the C-7 and C-8 positions of sialic acid residues in the polysaccharide (PS) . The immune response in mice was highly dependent on the degree of O-acetylation . Less O-acetylation resulted in higher serum bactericidal activity (SBA) towards the O-acetylated (OA) meningococcal strain, C11 . In addition, since an unconjugated de-O-acetylated (dOA) GCMP vaccine was previously shown to be highly immunogenic in humans, we had chosen this dOA form to couple with TT by reductive amination for clinical evaluation . This conjugate vaccine was shown to be well-tolerated and highly immunogenic in adults, children, and infants in the UK . To understand the nature of the GCMP protective epitope, a series of spectroscopic and serological studies were conducted, using high resolution H-NMR spectroscopy at 500 MHz and competitive inhibition SBA assays . The dOA GCMP was 10-1000 times better at inhibiting the SBA for an OA strain than the OA GCMP, suggesting that the GCMP-based protective epitope on the bacterium exists in a dOA form . In addition, SBA for an OA strain is highly correlated with dOA GCMP-specific IgG . NMR data on freshly isolated GCMP indicated that, on the surface of the organism, most of the O-acetylation exists at position C-8, with some regions containing dOA or OA C-7 sialic acid . After extraction of PS and storage in solution, most of the O-acetyl groups migrate to C-7, leaving an epitope that is conformationally related, but not quite identical (due to the presence of the O-acetyl group), to the one contained in the dOA PS . We speculate that the role of the O-acetyl group at the C-8 position of the PS on the organism is to form less immunogenic epitopes, or mask the protective epitope, and thus escape immune surveillance . The dOA form of the vaccine may therefore provide better protection against group C meningococcal disease than the OA form by eliciting a greater proportion of functional antibodies that are directly aimed at the protective epitope. Dev Biol (Basel), 2000, 103, 139 - 50 Monitoring stability of meningococcal group C conjugate vaccines; correlation of physico-chemical methods and immunogenicity assays; Ho MM et al.; Two meningococcal C-CRM197 conjugates differing in oligosaccharide chain length, number of conjugation sites, conjugation chemistry and process were monitored for stability at various temperatures or after repeated freeze-thawing by physico-chemical assays . The results were compared with assessment of immunogenicity in mice, previously shown to correlate with performance of the vaccine in clinical trials . The structural stability of the oligosaccharide chains and the protein carrier varied between the two types of conjugates . Neither was adversely affected by repeated freeze-thawing but one developed conformational changes in the protein carrier, detected by optical (CD, fluorescence) and NMR spectroscopy, when incubated at 23 degrees C or above, although integrity of the oligosaccharide structure was maintained . This was not associated with any reduction in primary IgM or IgG antibody responses to meningococcal C polysaccharide . Exposure to more extreme conditions resulting in release of a substantial proportion of free saccharide from the other conjugate sample was accompanied by significant reduction in both IgG and IgM antibody responses . In conclusion, FPLC-SEC, HPAEC-PAD and NMR spectroscopy were found useful for monitoring the stability of meningococcal C-CRM197 conjugates . Although optical spectroscopy was a sensitive method for detecting modification of the protein carrier, the results did not correlate with reduced immunogenicity. Lancet, 2001 Jan 20, 357(9251), 195 - 6 Efficacy of meningococcal serogroup C conjugate vaccine in teenagers and toddlers in England; Ramsay ME et al.; The UK was the first country to use meningococcal serogroup C conjugate (MCC) vaccines, which were licensed on the basis of immunogenicity and safety data but without a formal efficacy study . Increased surveillance during the first 9 months since introduction has shown that short-term efficacy of the MCC vaccine in England was 97% (95% CI 77-99) for teenagers and 92% (65-98) for toddlers . These early results confirm the superiority of MCC over plain C polysaccharide vaccines, which are ineffective in young children. Minerva Pediatr, 2000 Nov, 52(11), 659 - 60 Early onset neonatal sepsis due to Neisseria meningitidis B; Casanova-Roman M et al.; The onset of meningococcal infection in the first 72 hours after birth has only been reported on a few occasions; The authors describe a case where it was confirmed that the bacteria responsible, Neisseria meningitidis group B, grew in the newborn's blood and in the mother's lochia . The transmission mechanisms are also reviewed. Ann Ital Med Int, 2000 Oct-Dec, 15(4), 291 - 5 {Meningococcal meningitis in the adult complicated by cutaneous necrosis: description of a clinical case}; Porro F et al.; Meningitis and meningococcal sepsis are emergency conditions associated with high mortality . The outcome is worsened by the onset of disseminated intravascular coagulation . This may present, particularly in children, with the clinical picture of purpura fulminans, characterized by extensive necrotic-hemorrhagic skin lesions, ischemia of the extremities and multiorgan failure . It has been observed that depletion of coagulation inhibitors, particularly protein C, plays a key role in the development of this severe complication . We describe the case of a woman who presented in the Emergency Room with signs of meningitis, drowsiness, hypotension and petechie . Bacterioscopic examination of the cerebrospinal fluid evidenced characteristic gram-negative diplococci . Laboratory data disclosed initial disseminated intravascular coagulation with low levels of proteins C and S . Following intravenous infusion of antibiotics, fluids and fresh frozen plasma, the patient's condition rapidly improved . However, multiple skin lesions appeared on her fingers, toes and heels . It is likely that the infusion of coagulation inhibitors contained in fresh frozen plasma, prevented evolution to full-blown purpura fulminans . The first choice treatment for purpura fulminans in meningococcal sepsis is infusion of protein C concentrate, which is not, however, currently available on the market. Sex Transm Dis, 2001 Jan, 28(1), 29 - 32 An unusual transmission of Neisseria meningitidis: neonatal conjunctivitis acquired at delivery from the mother's endocervical infection; Fiorito SM et al.; BACKGROUND: Primary meningococcal conjunctivitis is assumed to be due to the direct inoculation of Neisseria meningitidis into the conjunctival sac from an exogenous source . According to a literature review, no case of neonatal conjunctivitis infection acquired at delivery from maternal endocervicitis has been published . GOAL: To report a case of meningococcal neonatal conjunctivitis acquired at delivery because of the mother's endocervical infection and cross-transmission of the strain with her partner . STUDY DESIGN: Strains were characterized by bacteriologic and serologic methods including grouping (agglutination), typing, and subtyping (enzyme-linked immunoabsorbent assay) . Molecular analysis was done by pulsed-field gel electrophoresis . RESULTS: The three strains (newborn infant, mother, partner) were of the same antigenic formula (C:NT:P1.NT) and exhibited similar NheI and SpeI pulsed-field gel electrophoresis patterns . CONCLUSION: The identical phenotypic and genomic analysis of strains is the evidence for N meningitidis transmission at delivery from a maternal endocervical infection to the newborn infant and cross transmission between sexual partners. Lancet . 2000 Dec 23-30;356(9248):2159. Serogroup W135 meningococcal disease in Hajj pilgrims; Taha MK et al.; An outbreak of W135 meningococcal disease occurred in the spring of 2000 among pilgrims returning from Saudi Arabia and their contacts . Clinical isolates from England and France were examined and compared with reference strains from other countries . Characterisation of isolates by a range of typing methods showed them to be of clonal origin (ET-37) and closely related to other meningococci with an established propensity to cause disease clusters . A reappraisal of vaccination strategies for travellers is required. Commun Dis Intell, 2000 Nov, 24(11), 332 - 5 Enhanced surveillance for meningococcal disease in Queensland in 1999; Ward J et al.; Enhanced surveillance of invasive meningococcal disease commenced in Queensland in 1999 . There were 93 cases, an incidence of 2.8/100,000 population . Most (87%) cases were laboratory confirmed, but 12 per cent were probable cases without laboratory confirmation . The highest age-specific attack rates were in the under 1, 1 to 4 and 15 to 24 year age groups . Most of the serologically characterised isolates were group B (70%), followed by group C (24%) . There were 12 deaths, resulting in a case fatality rate of 13 per cent . Those who died were more likely to have group C than group B disease (OR 5.04, CI 1.05-25.14) . Only 14 per cent of cases that saw a general practitioner (GP) prior to hospitalization received parenteral antibiotics, 23 per cent of the 35 cases referred to hospital by a GP received pre-hospital parenteral antibiotics and 33 per cent of cases were notified to health authorities within 24 hours of hospital admission . Thirty per cent were notified two or more days after hospitalization, delaying the start of public health action . Enhanced surveillance has demonstrated a need to promote the use of pre-hospital parenteral antibiotics by GPs and a need to encourage more timely reporting of cases to health authorities. J Bacteriol, 2001 Feb, 183(3), 934 - 41 Analysis of lipooligosaccharide biosynthesis in the Neisseriaceae; Arking D et al.; Neisserial lipooligosaccharide (LOS) contains three oligosaccharide chains, termed the alpha, beta, and gamma chains . We used Southern hybridization experiments on DNA isolated from various Neisseria spp . to determine if strains considered to be nonpathogenic possessed DNA sequences homologous with genes involved in the biosynthesis of these oligosaccharide chains . The presence or absence of specific genes was compared to the LOS profiles expressed by each strain, as characterized by their mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel and their reactivities with various LOS-specific monoclonal antibodies . A great deal of heterogeneity was seen with respect to the presence of genes encoding glycosyltransferases in Neisseria . All pathogenic species were found to possess DNA sequences homologous with the lgt gene cluster, a group of genes needed for the synthesis of the alpha chain . Some of these genes were also found to be present in strains considered to be nonpathogenic, such as Neisseria lactamica, N . subflava, and N . sicca . Some nonpathogenic Neisseria spp . were able to express high-molecular-mass LOS structures, even though they lacked the DNA sequences homologous with rfaF, a gene whose product must act before gonococcal and meningococcal LOS can be elongated . Using a PCR amplification strategy, in combination with DNA sequencing, we demonstrated that N . subflava 44 possessed lgtA, lgtB, and lgtE genes . The predicted amino acid sequence encoded by each of these genes suggested that they encoded functional proteins; however, structural analysis of LOS isolated from this strain indicated that the bulk of its LOS was not modified by these gene products . This suggests the existence of an additional regulatory mechanism that is responsible for the limited expression of these genes in this strain. Med Sci Monit, 2000 Sep-Oct, 6(5), 1008 - 12 Subdural empyemas--a rare complication of meningococcal cerebrospinal meningitis in children; Bako W et al.; Subdural empyemas are a rare, life-threatening complication of cerebrospinal meningitis . Two cases of subdural empyemas which occurred as early complications after cerebrospinal meningitis in infants are presented . Utilization of modern diagnostic methods, such as US and CT allowed to establish an early diagnosis, which made it possible to institute appropriate treatment, involving evacuation of the purulent content with local application of antibiotics followed by intravenous antibiotics well penetrating the fluid-filled compartments of the CNS . Early institution of treatment gave a chance of complete recovery in both presented cases. An Esp Pediatr, 2001 Jan, 54(1), 65 - 8 {Meningococcal disease . new prevention strategies}; Soult Rubio JA et al.; Because conjugate C meningococcal vaccines represent a significant advance in the prevention of meningococcal disease, currently accepted recommendations on vaccination should be revised . The health authorities are responsible for carrying out national surveillance programs and for evaluating the need for vaccination programs . These programs should target all groups at risk for this disease and should confer adequate and lasting protection in vaccinated children. Infect Immun, 2001 Mar, 69(3), 1971 - 3 Circumvention of herd immunity during an outbreak of meningococcal disease could be correlated to escape mutation in the porA gene of Neisseria meningitidis; Taha MK et al.; Meningococcal strains isolated during an outbreak were shown to belong to the ET-5 complex and to harbor a mutation in the VR2 region of the porA gene . They were less susceptible to the bactericidal effect of normal human serum than was the ET-5 wild-type strain . These results are of concern, as PorA is a potential target in vaccine design. Infect Immun, 2001 Mar, 69(3), 1816 - 20 NmeSI restriction-modification system identified by representational difference analysis of a hypervirulent Neisseria meningitidis strain; Bart A et al.; Neisseria meningitidis is a gram-negative bacterium that may cause meningitis, sepsis, or both . The increase in the incidence of meningococcal disease in various countries in the past 2 decades is mainly due the genotypically related lineage III meningococci . The chromosomal DNA differences between lineage III strains and non-lineage III strains were identified using representational difference analysis . Thus, a 1.8-kb locus that is specific for lineage III meningococci was identified . The locus contains three open reading frames encoding the NmeSI restriction-modification system . The methyltransferase gene was cloned and expressed in Escherichia coli . Site AGTACT was found to be modified by the enzyme . In conclusion, lineage III strains differ from endemic strains by the presence of a specific restriction-modification system . This restriction-modification system may contribute to the clonal and hypervirulent character of lineage III strains by influencing horizontal gene transfer and transcription. Infect Immun, 2001 Mar, 69(3), 1687 - 96 exl, an exchangeable genetic island in Neisseria meningitidis; Kahler CM et al.; The genetic structure and evolution of a novel exchangeable meningococcal genomic island was defined for the important human pathogen Neisseria meningitidis . In 125 meningococcal strains tested, one of three unrelated nucleotide sequences, designated exl (exchangeable locus), was found between a gene required for heme utilization, hemO, and col, encoding a putative Escherichia coli collagenase homologue . The 5' boundary of each exl cassette was the stop codon of hemO, whereas the 3' boundary was delineated by a 33-bp repeat containing neisserial uptake sequences located downstream of col . One of the three alternative exl cassettes contained the meningococcal hemoglobin receptor gene, hmbR (exl3) . In other meningococcal strains, hmbR was absent from the genome and was replaced by either a nucleotide sequence containing a novel open reading frame, exl2, or a cassette containing exl3 . The proteins encoded by exl2 and exl3 had no significant amino acid homology to HmbR but contained six motifs that are also present in the lipoprotein components of the lactoferrin (LbpB), transferrin (TbpB), and hemoglobin-haptoglobin (HpuA) uptake systems . To determine the evolutionary relationships among meningococci carrying hmbR, exl2, or exl3, isolates representing 92 electrophoretic types were examined . hmbR was found throughout the population structure of N . meningitidis (genetic distance, >0.425), whereas exl2 and exl3 were found in clonal groups at genetic distances of <0.2 . The commensal neisserial species were identified as reservoirs for all of the exl cassettes found in meningococci . The structure of these cassettes and their correlation with clonal groups emphasize the extensive gene pool and frequent horizontal DNA transfer events that contribute to the evolution and virulence of N . meningitidis. Infect Immun, 2001 Mar, 69(3), 1568 - 73 Serological basis for use of meningococcal serogroup C conjugate vaccines in the United Kingdom: reevaluation of correlates of protection; Borrow R et al.; The antibody data supporting the use of meningococcal serogroup C conjugate (MCC) vaccines in the United Kingdom were generated by serum bactericidal assay (SBA) using rabbit complement (rSBA) . This may give higher titers than those obtained with human complement (hSBA), for which the "gold standard" correlate of protection for meningococcal C disease is a titer of > or =4 . Comparison of rSBA and hSBA titers in sera from unvaccinated adults with an rSBA titer of > or =8 showed that for 93% (27 of 29) the titer was > or =4 by hSBA, confirming natural protection . Furthermore, sera from MCC vaccinees showed that an rSBA titer of <8 or > or =128 discriminated susceptibility and protection well (85% with rSBA titers of <8 had hSBA titers of <4, and 99% with rSBA titers of > or =128 had hSBA titers of > or =4) . However, discrimination was poor in the rSBA titer range 8 to 64, with only 60% having hSBA titers of > or =4 . In such cases we propose that protection can be assumed if there is a fourfold rise in titer between pre- and postvaccination sera or if there is a characteristic booster response to a polysaccharide challenge dose with, if available, evidence of antibody avidity maturation or an hSBA titer of result > or =4 . Applying these criteria to toddlers, 10 to 40% of whom had titers in the range 8 to 64 after a single dose of MCC vaccine, showed that 94% had a fourfold rise in titer, including 98% of those in the titer range 8 to 64 . In addition, of those with titers of <128 post-MCC vaccination, 90% had titers of > or =128 after a 10-microg polysaccharide booster dose, compared with only 7% of unprimed age-matched toddlers given a full 50-microg dose . Furthermore, the increase in geometric mean avidity index pre- and postbooster was independent of post-primary MCC titer . These results indicated that the majority of toddlers with an rSBA titer between 8 and 64, and some of those with an hSBA result of <4, have mounted a protective immune response with the induction of immunological memory. Infect Immun, 2001 Mar, 69(3), 1561 - 7 Recombinant Neisseria meningitidis transferrin binding protein A protects against experimental meningococcal infection; West D et al.; To better characterize the vaccine potential of Neisseria meningitidis transferrin binding proteins (Tbps), we have overexpressed TbpA and TbpB from Neisseria meningitidis isolate K454 in Escherichia coli . The ability to bind human transferrin was retained by both recombinant proteins, enabling purification by affinity chromotography . The recombinant Tbps were evaluated individually and in combination in a mouse intraperitoneal-infection model to determine their ability to protect against meningococcal infection and to induce cross-reactive and bactericidal antibodies . For the first time, TbpA was found to afford protection against meningococcal challenge when administered as the sole immunogen . In contrast to the protection conferred by TbpB, this protection extended to a serogroup C isolate and strain B16B6, a serogroup B isolate with a lower-molecular-weight TbpB than that from strain K454 . However, serum from a TbpB-immunized rabbit was found to be significantly more bactericidal than that from a TbpA-immunized animal . Our evidence demonstrates that TbpA used as a vaccine antigen may provide protection against a wider range of meningococcal strains than does TbpB alone . This protection appears not to be due to complement-mediated lysis and indicates that serum bactericidal activity may not always be the most appropriate predictor of efficacy for protein-based meningococcal vaccines. JAMA, 2001 Jan 10, 285(2), 177 - 81 Effectiveness of a mass immunization campaign against serogroup C meningococcal disease in Quebec; De Wals P et al.; CONTEXT: An outbreak of meningococcal disease in Quebec province prompted a mass immunization program . The impact of this campaign on the epidemiology of meningococcal disease has not been studied . OBJECTIVES: To study the impact of a mass immunization campaign using polysaccharide vaccine on the epidemiology of meningococcal disease (MCD) and to assess serogroup C vaccine effectiveness (VE) . DESIGN, SETTING, AND SUBJECTS: Analysis of MCD cases reported in Quebec from 1990 to 1998, before and after the mass immunization campaign was conducted during the winter of 1992-1993, when 84% of residents aged 6 months to 20 years (the target population, approximately 1.9 million individuals) were vaccinated . MAIN OUTCOME MEASURES: Incidence of MCD in 1990-1998; incidence of culture-proven serogroup C MCD between April 1, 1993, and March 31, 1998, compared among vaccinated and unvaccinated persons in the target population . RESULTS: The incidence of serogroup C disease decreased after the mass immunization campaign, from 1.4 per 100 000 in 1990-1992 to 0.3 per 100 000 in 1993-1998, and the overall incidence of other serogroups remained stable at 0.7 per 100 000, with a small increase in the proportion of cases caused by serogroup Y (P =.009) . Protection from serogroup C MCD was indicated in the first 2 years after vaccine administration (VE, 65%; 95% confidence interval {CI}, 20%-84%), but not in the next 3 years (VE, 0%; 95% CI, -5% to 65%) . Vaccine effectiveness was strongly related to age at vaccination: 83% (95% CI, 39%-96%) for ages 15 through 20 years, 75% (95% CI, - 17% to 93%) for ages 10 through 14 years, and 41% (95% CI, -106% to 79%) for ages 2 through 9 years . There was no evidence of protection in children younger than 2 years; all 8 MCD cases in this age group occurred in vaccinees . CONCLUSIONS: Serogroup C polysaccharide vaccine is effective for controlling outbreaks in teenaged individuals but should not be used in children younger than 2 years . The mass campaign did not induce significant serogroup switching. Rev Saude Publica, 2000 Dec, 34(6), 589 - 95 {Fatality rate in the epidemiology of meningococcal disease: study in the region of Campinas, SP, Brazil, 1993 to 1998}; Donalisio MR et al.; OBJECTIVE: To analyze the trends of the meningococcal disease cumulative incidence and case-fatality rate in the region of Campinas, Brazil, an area that encircles five cities and 1.2 million inhabitants, from 1993 to 1998 . METHODS: A longitudinal retrospective study of all case records (375) obtained from the regional epidemiological surveillance system was carried out . A logistic regression analysis allowed identifying the risk factors related to fatal outcomes of meningococcal disease . RESULTS: The highest fatality rates (23.8%) were seen in the period of 1996 and 1997, coinciding with the incidence peaks of serogroup B Neisseria and a high percentage of septicemia cases . Also at the same period there was registered a poor etiological investigation of the cases . A seasonal pattern and the predomination of strains B:4:P1.15 and C:2b:P1.3 were observed . In the logistic regression analysis, the risk factors related to fatality were: septicemia with or without meningitis (adjusted odds ratio {OR(aj)} = 13.88 and 95% confidence interval {CI} = 4.68 - 42.13); age over 30 years (OR(aj) = 6.42; CI = 2.32 - 17.80); age under 1 year (OR(aj) = 2.95; CI = 1.55 - 5.63); and serogroup B (OR(aj) = 2.33; CI = 1.14 - 4.79) . CONCLUSIONS: Septicemia, age and serogroup were predictive variables related to a fatal outcome . In 1996 and 1997, case-fatality rates were high, indicating the need to further assessment of the quality of the services delivered and their readiness to take preventive action . The lack of etiological identification in many cases precluded more accurate inferences about the epidemiological behavior of Neisseria meningitidis in the region. Curr Opin Microbiol, 2001 Feb, 4(1), 47 - 52 Meningococcal pathogenesis: at the boundary between the pre- and post-genomic eras; Tinsley C et al.; Meningococcal disease remains an important public health burden worldwide and, indeed, cause of death, particularly in poorer countries . The rapidly progressive nature of infections means that antibiotic therapy often comes too late . Vaccines are of limited efficacy in infants, one of the most vulnerable age groups, and do not exist for bacteria of serogroup B . Hence, much remains to be achieved in terms of vaccine design and the understanding of the pathogenesis of meningococcal disease . The causative bacterium, Neisseria meningitidis, is usually a commensal of the nasopharynx . Factors that lead to the invasion of the bloodstream, often followed by the crossing of the blood-brain barrier and meningitis, may be partly host- and partly bacterium-dependent, but are ill-understood . It is hoped that, taken together with the fundamental knowledge gained from biochemical and genetic studies, the huge amount of new information made available with the recent publication of the genome sequences will help to unlock more of the secrets of the lifestyle and pathogenic potential of this still poorly understood pathogen. Clin Microbiol Infect, 2000 May, 6(5), 259 - 62 Increasing microbiological confirmation and changing epidemiology of meningococcal disease on Merseyside, England; Carrol ED et al.; OBJECTIVES: To determine, for the last 5 years in children on Merseyside with clinical meningococcal disease (MCD), the impact on diagnostic yield of newer bacteriologic methods; bacterial antigen detection (AD) and polymerase chain reaction (PCR) . METHODS: Prospective data collection at Royal Liverpool Children's Hospital over two epochs: 1 September 1992 to 30 April 1994 (epoch A, n = 126) and 17 November 1997 to 15 September 1998 (epoch B, n = 85) . RESULTS: Epoch A was compared with epoch B . Diagnosis was confirmed by detection of meningococci in 78 of 126 (61.9%) versus 64 of 85 (75.3%, P = 0.04), but with a significantly lower rate of positive blood and cerebrospinal fluid culture in the later epoch . The proportion of cases receiving penicillin pretreatment was unchanged at 32%, but the proportion undergoing lumbar puncture decreased significantly . Median ages were higher in epoch B: 1.7 years versus 2.49 years (P = 0.013, Mann-Whitney) . There was a significant increase in the proportion of cases due to serogroup C (14/78 (18%) versus 30/64 (46.9%), P = 0.001) . CONCLUSIONS: Culture detection of meningococci from children with MCD has reduced, as less lumbar punctures are done . However, improved diagnosis by PCR and AD has increased microbiological confirmation overall . Serogroup C disease and the median age of cases continue to rise. Clin Microbiol Infect, 2000 Jan, 6(1), 29 - 33 Use of an automated DNA analysis system (DARAS) for sequence-specific recognition of Neisseria meningitidis DNA; Seward RJ et al.; OBJECTIVES: To combine use of the polymerase chain reaction (PCR) for rapid diagnosis of meningococcal meningitis with a novel automated detection system for sequence-specific recognition of PCR products . METHODS: DNA was extracted from cerebrospinal fluid (CSF) by a quick boil-lysis method, followed by PCR with primers specific for Neisseria meningitidis . Sequence-specific recognition of N . meningitidis DNA was performed with an automated DNA analysis system (DARAS) and the data were compared with results following agarose gel electrophoresis or conventional microbiological culture . RESULTS: The DARAS system had a sensitive detection limit of 102 meningococci/mL with spiked samples, compared with a detection limit of 104 meningococci/mL following agarose gel electrophoresis . When the system was used to examine 74 CSF samples, the 19 CSF samples positive for N . meningitidis by conventional microbiological methods were also all positive in the DARAS system and the 55 samples negative by DARAS for meningococci were also negative by conventional microbiological methods . CONCLUSION: The sensitivity and specificity of the DARAS system makes it a useful tool for the diagnosis of meningococcal meningitis . The system is user-friendly, requires minimal hands-on time and generates data in an informative numerical format. APMIS, 2000 Jul-Aug, 108(7-8), 509 - 16 Genosubtyping by sequencing group A, B and C meningococci; a tool for epidemiological studies of epidemics, clusters and sporadic cases; Molling P et al.; Genosubtyping, by sequencing variable regions (VRs) 1, 2 and 3 of the porA gene, was evaluated as a tool to detect clonality of isolates in meningococcal epidemics in Africa and clusters of disease in Sweden . All 63 examined meningococcal isolates were successfully genosubtyped . The isolates belonging to group A type 4 with genosubtype P1.20,9,35a showed little heterogeneity in African epidemics in 1988 and onwards . In Sweden, two meningococcal clones of group B type 15, with genosubtypes P1.7,16,35 and P1.7,16f,35, dominated during two clusters of meningococcal disease in 1995-96 and in sporadic cases thereafter . The characterisation of group C meningococci isolated during 1992 in Sweden indicated a cluster (type 2a with genosubtype P1.5a,10d,36b) connected with a discotheque visit . Two variants of VR2 (10p and 25b), not previously described, were found among the examined isolates . Nucleotide sequence analysis of VRs in the porA gene proved a valuable epidemiological tool since almost all isolates could be genosubtyped, in contrast to the phenotypic methods presently used. Int J Pediatr Otorhinolaryngol, 2001 Feb, 57(2), 161 - 4 Meningococcal septicemia post adenotonsillectomy in a child: case report; Guirguis M et al.; Hemorrhage, nausea and vomiting and poor oral intake remain the most commonly encountered complications after adenotonsillectomy in the pediatric population . Life-threatening infectious complications such as meningitis have rarely been reported . We report a case of meningococcal septicemia complicating adenotonsillectomy in a 3-year-old male child . Possible etiologies postulated include: septicemia following transient bacteremia, increased meningococcal carrier rate, transient immune deficiency, and mucosal damage promoting bacterial translocation . This case highlights the responsibility of the otolaryngologist to maintain medical review, especially when recovery following TA is slow. Vaccine, 2001 Jan 8, 19(11-12), 1327 - 46 Development of natural immunity to Neisseria meningitidis; Pollard AJ et al.; Although meningococcal disease is rare in industrialized nations, Neisseria meningitidis holds a prominent position amongst pediatric infections because of the dramatic clinical presentation of the disease, high mortality, epidemic potential and the recent disappearance of many other important infectious diseases in developed countries through improvements in public health and vaccination . The precise nature of natural immunity to meningococci remains unknown, although a complex interaction between the organism and nasopharyngeal mucosal barrier, innate immune mechanisms and acquired immunity is involved . Study of the mechanisms of natural immunity may provide the key to development of vaccines that can reduce the burden of disease in early childhood. J Bacteriol, 2001 Feb, 183(4), 1233 - 41 A putatively phase variable gene (dca) required for natural competence in Neisseria gonorrhoeae but not Neisseria meningitidis is located within the division cell wall (dcw) gene cluster; Snyder LA et al.; A cluster of 18 open reading frames (ORFs), 15 of which are homologous to genes involved in division and cell wall synthesis, has been identified in Neisseria gonorrhoeae and Neisseria meningitidis . The three additional ORFs, internal to the dcw cluster, are not homologous to dcw-related genes present in other bacterial species . Analysis of the N . meningitidis strain MC58 genome for foreign DNA suggests that these additional ORFs have not been acquired by recent horizontal exchange, indicating that they are a long-standing, integral part of the neisserial dcw gene cluster . Reverse transcription-PCR analysis of RNA extracted from N . gonorrhoeae strain FA19 confirmed that all three ORFs are transcribed in gonococci . One of these ORFs (dca, for division cluster competence associated), located between murE and murF, was studied in detail and found to be essential for competence in the gonococcal but not in the meningococcal strains tested . Computer analysis predicts that dca encodes an inner membrane protein similar to hypothetical proteins produced by other gram-negative bacteria . In some meningococcal strains dca is prematurely terminated following a homopolymeric tract of G's, the length of which differs between isolates of N . meningitidis, suggesting that dca is phase variable in this species . A deletion and insertional mutation was made in the dca gene of N . gonorrhoeae strain FA19 and N . meningitidis strain NMB . This mutation abrogated the ability of the gonococci to be transformed with chromosomal DNA . Thus, we conclude that the dca-encoded gene product is an essential competence factor for gonococci. J Antimicrob Chemother, 2001 Feb, 47(2), 219 - 22 Rifampicin-resistant meningococci causing invasive disease: detection of point mutations in the rpoB gene and molecular characterization of the strains; Stefanelli P et al.; Mutations in the rpoB gene affecting two amino acids were found in eight rifampicin-resistant Neisseria meningitidis group B and C strains isolated in Italy . The Asp542-->Val substitution, documented for the first time in N . meningitidis, was found in four of the isolates; the His552-->Tyr or Asn substitution in the other four resistant strains . Mutations in the mtr gene did not seem to be involved in the resistance since the same mutations occurred in both resistant and susceptible strains . Two different clusters were identified among these resistant strains, without any correlation with the specific mutations detected in the rpoB gene. Rev Med Chil, 1999 Sep, 127(9), 1086 - 92 {Non linear analysis of infection diseases dynamics in Chile}; Canals M et al.; BACKGROUND: The incidence of infectious diseases generally has large fluctuations, probably due to interactions between seasonal fluctuations and those secondary to case-susceptible host interactions . AIM: To analyze the complexity and attractant topological resemblance of seven infectious diseases in Chile . MATERIAL AND METHODS: The annual incidence of measles, whooping cough, scarlet fever, meningococcal meningitis, diphtheria, typhoid fever and poliomyelitis was obtained from the annual reports of diseases . Correlation dimensions and the largest Lyapunov series exponents were estimated . The resemblance among their attractants was assessed by Hausdorff distance . The measures were performed both before and after seasonal filtering . RESULTS: All series showed a dynamics near low dimensional chaos . The correlation dimensions ranged between 2.12 and 2.76 . The correlation dimensions did not change after seasonal differentiation . Apart from one, all disease dynamics had large Lyapunov exponents, near 0.6 Bits/year . These decreased if series were differentiated . Before differentiation, the topological resemblance was mainly caused by the seasonal component of the dynamics but thereafter, the resemblance increased . In spite of different transmission mechanisms and etiologies, all analyzed infectious diseases conformed a truly single group, during cluster analyses . CONCLUSIONS: These results suggest that beneath the dynamics of infectious diseases, obscured by seasonal environmental factors, lays a very consistent nonlinear agent-susceptible host dynamics. Med Dosw Mikrobiol, 2000, 52(3), 257 - 66 {Characterization of Neisseria meningitidis strains isolated from carriers}; Grzybowska W et al.; Neisseria meningitidis carriers strains were isolated from 17-19 teenagers (n = 14) and recruits (n = 267) . The longitudinal study comprises three meningococcal carriage trials performed on healthy young men during two--six months of their service in Polish military units . Altogether 54, 124 and 89 meningococcal strains were obtained during spring 1998 and autumn 1998, 1999 trials . Sixty two percent of meningococcal carrier strains were non-groupable, however among the remaining strains, serogroup B was predominant (29.5%) . During spring 1998 and autumn 1999 trials the predominant phenotypes were N . meningitidis NG:21:P1.7, but during the autumn 1998 NG:21:P1.7 or NG:NT:P1.5 . Ribotyping of type 21 and/or subtype P1.7 strains (n = 27) showed presence of 2 main ribotypes . Pulsed Field Gel Electrophoresis of consecutive isolates recovered from the same carrier showed great similarity of the patterns. Med Dosw Mikrobiol, 2000, 52(3), 247 - 55 {Tests for Neisseria meningitidis in adolescents and adults (recruits)}; Tyski S et al.; No N . meningitidis strain was isolated from 168 children 14 years old . However, among 17-19 years old young people 14% meningococcal carriage rate was demonstrated . In three surveillance trials performed in military units in spring 1998 and autumn 1998 and 1999; 81, 225 and 153 isolates of N . meningitidis, respectively were obtained . A change in N . meningitidis carrier status was observed . At the autumn study, two times more N . meningitidis intermittent carriers were found than in the spring investigations . Among these population we found short-term and long-term carriers--last day of the longest trial--162 day . Meningococcal carriage rate increases among recruits in overcrowded living conditions. Cytokine, 2001 Jan 21, 13(2), 91 - 7 Outer membrane vesicles from Neisseria meningitidis: effects on cytokine production in human whole blood; Mirlashari MR et al.; The Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine consists of outer membrane proteins (OMPs) as main antigens with significant amounts of lipopolysaccharide (LPS; 5-9% relative to protein) . We have studied the ability of this OMV vaccine preparation to induce secretion of pro-inflammatory cytokines, tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8) and anti-inflammatory cytokines, interleukin 4 (IL-4), interleukin 10 (IL-10) and interleukin 13 (IL-13) in a human whole blood model . Plasma levels of TNF-alpha, IL-1beta, IL-6 and IL-8 were massively increased; mean peak levels of TNF-alpha 44 696+/-7764, IL-1beta 38 043+/-5411, IL-6 10 057+/-1619 and IL-8 30 449+/-5397 pg/ml were obtained with an OMV-LPS concentration of 1 microg/ml; corresponding levels in control plasmas were below the detection limit of the assay . Mean maximal level of IL-10 (2540+/-144 pg/ml) was obtained at OMV-LPS concentration of 10 microg/ml, after 24 h; while the level in control plasma was below detection limit . OMV-LPS did not induce release of IL-4 and IL-13 in doses from 0.001-10 microg/ml . The present results show that OMVs from meningococci have potent pro-inflammatory properties and are likely to contribute to the observed local and systemic inflammatory effects . Lancet, 2000 Dec 16, 356(9247), 2065 - 6 Production of low-avidity antibody by infants after infection with serogroup B meningococci; Pollard AJ et al.; Experimental serogroup B meningococcal vaccines have induced only poor immune responses and have had little protective efficacy in children younger than 1 year of age . We used ELISA with potassium thiocyanate to compare the average avidity of antibody produced by infants with that of children older than 10 years after systemic disease . Infants produced specific antibody of lower average avidity than older children--a finding that correlates with absence of serum bactericidal activity in the serum samples of the same infants. Schweiz Rundsch Med Prax, 2000 Nov 23, 89(47), 1959 - 62 {Wxanthema and acute polyarthritis in a young patient}; Germann D et al.; A young woman developed acute polysynovitis and vasculitis-like changes to the skin . Her blood cultures were positive for Neisseria meningitidis, enabling us to diagnose chronic meningococcemia . This finding was a surprise; in retrospect this diagnosis would not have been expected in light of the fact that there was no meningism, the patient's general condition was only slightly diminished and the temperatures were subfebrile . Besides an episode of vasculitis, the primary differential diagnosis of acute polysynovitis in young women should include a bacterial infection, for example with Neisseria . Usually, Neisseria gonorrhoeae (gonococci) are involved and, as in the case described, only very rarely Neisseria meningitidis (meningococci) . The present case report is given to illustrate new clinical aspects of known, but rare disease, to remind clinicians to consider the differential diagnosis of acute polyarthritis and to generate discussion about the clinical signs and pathogenesis of reactive arthritides, in particular, Neisseria. Nurs Crit Care, 2000 Mar-Apr, 5(2), 87 - 97 Use of a theoretical framework in paediatric intensive care to provide support for parents of children with severe meningococcal disease; Haines C; The impact on parents of having a child admitted to a paediatric intensive care unit (PICU) with meningococcal disease (MD) is discussed . Analysis, synthesis and evaluation of how nurses within a PICU can use a theoretical framework to identify and facilitate a decision-making process, regarding the support required by the parents of these children, is outlined . Peplau's interpersonal/conceptual framework is used as a basis for the investigation. Int J Antimicrob Agents, 2001 Jan, 17(1), 27 - 31 Meningococcal disease in Slovenia (1993-1999): serogroups and susceptibility to antibiotics . Slovenian Meningitis Study Group; Cizman M et al.; The epidemiology of meningococcal disease was studied prospectively in Slovenia from 1993 to 1999 in children and from 1995 to 1999 in adults . Patients with meningococci isolated from normally sterile body sites were included in the study . Altogether 75 patients (57 children, 18 adults) were found with meningococcal diseases . The overall yearly incidence was 0.43 per 100000 inhabitants . The highest annual incidence (18.5/100000) was found in children between 1 month and 1 year of age . The case to fatality ratio was 4.1% . Group B meningococci were isolated most frequently (84.7%), followed by group C (11.1%) . In six patients (8.3%) isolates were less susceptible to penicillin . Four of these were successfully treated with penicillin alone. Vaccine, 2000 Dec 8, 19(9-10), 1232 - 8 A randomised, double-blind, controlled trial of the immunogenicity and tolerability of a meningococcal group C conjugate vaccine in young British infants; English M et al.; A double-blind, randomised, controlled trial was conducted in 248 British infants to assess the immunogenicity and tolerability of three doses of a meningococcal group C/CRM (197) conjugate vaccine (Lederle Laboratories, USA) given at 2, 3 and 4 months . Control children received three doses of Hepatitis B vaccine (Engerix B(R); SmithKline Beecham) . At 5 months of age, 100% of children receiving the conjugate vaccine had specific immunoglobulin G concentrations >2.0 microg/ml (n=116) compared with only 4% of control children (n=121) . Those receiving the conjugate also had 2.5- and 1.6-fold higher geometric mean concentrations of PRP and diphtheria antibodies, respectively . The vaccine was well tolerated. Vaccine, 2000 Dec 8, 19(9-10), 1141 - 8 Immunogenicity and safety of monovalent p1.7(h),4 meningococcal outer membrane vesicle vaccine in toddlers: comparison of two vaccination schedules and two vaccine formulations; de Kleijn ED et al.; The safety and immunogenicity of two PorA-based meningococcal outer membrane vesicle (OMV) vaccines against the P1.4 serosubtype adsorbed with AlPO(4) or Al(OH)(3) were studied in 134 toddlers . Vaccinations were given three times with an interval of 3-6 weeks or twice with an interval of 6-10 weeks . A vaccination was repeated after 20-40 weeks . Pre- and post-immunization sera were tested for bactericidal activity against an isogenic strain expressing P1.7(h), 4 PorA . Both meningococcal OMV vaccines were well tolerated . The percentage of children with a fourfold increase in bactericidal activity was 96% (AlPO(4)-adjuvated vaccine/2+1 schedule), 100% (AlPO(4)-adjuvated vaccine/3+1 schedule), 93% (Al(OH)(3)-adjuvated vaccine/2+1 schedule) and 97% (Al(OH)(3)-adjuvated vaccine/3+1 schedule) . Adsorption with AlPO(4) makes the OMV vaccine more immunogenic than adsorption with Al(OH)(3) . Bactericidal activity was highest after the 3+1 schedule, although the response shortly after the primary series was higher in the two-dose priming group. Vaccine, 2000 Dec 8, 19(9-10), 1129 - 32 Reduced antibody response to revaccination with meningococcal serogroup A polysaccharide vaccine in adults; Borrow R et al.; Widespread use of meningococcal A and C polysaccharide (MACP) vaccines has raised concerns about induction of hyporesponsiveness to these polysaccharides . Immunological hyporesponsiveness to C polysaccharide has been clearly documented in infants, children and adults but only limited data from Gambian children are available for A polysaccharide . We investigated whether a second dose of MACP, given 6 months after an initial dose affected the immunological response as measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay (ELISA), to serogroup A meningococci in young adults (university students, n=36) . Serogroup A SBA responses 1 month following the second dose of MACP (geometric mean titre (GMT) 103.6, 95% CI 45.6-235.1) were approximately one third of the levels observed 1 month post first dose (GMT 281.9, 95% CI 134.9-581.4) . The serogroup A-specific IgG levels post second dose (GMC 21.2, 95% CI 15.3-29.4) were also significantly lower at an average of three-quarters the level post first dose (GMC 28.7, 95% CI 20.8-39.7) . This confirms that revaccination with MACP vaccine, 6 months following the initial dose, results in a reduced immunological response to A polysaccharide in adults . Repeated vaccination with MACP vaccine may be ineffective and development and use of meningococcal serogroup A conjugate vaccines should be encouraged. J Clin Microbiol, 2001 Jan, 39(1), 75 - 85 Evaluation of pulsed-field gel electrophoresis in epidemiological investigations of meningococcal disease outbreaks caused by Neisseria meningitidis serogroup C; Popovic T et al.; Since 1990, the frequency of Neisseria meningitidis serogroup C (NMSC) outbreaks in the United States has increased . Based on multilocus enzyme electrophoresis (MEE), the current molecular subtyping standard, most of the NMSC outbreaks have been caused by isolates of several closely related electrophoretic types (ETs) within the ET-37 complex . We chose 66 isolates from four well-described NMSC outbreaks that occurred in the United States from 1993 to 1995 to evaluate the potential of pulsed-field gel electrophoresis (PFGE) to identify outbreak-related isolates specific for each of the four outbreaks and to differentiate between them and 50 sporadic isolates collected during the outbreak investigations or through active laboratory-based surveillance from 1989 to 1996 . We tested all isolates collected during the outbreak investigations by four other molecular subtyping methods: MEE, ribotyping (ClaI), random amplified polymorphic DNA assay (two primers), and serotyping and serosubtyping . Among the 116 isolates, we observed 11 clusters of 39 NheI PFGE patterns . Excellent correlation between the PFGE and the epidemiological data was observed, with an overall sensitivity of 85% and specificity of 71% at the 95% pattern relatedness breakpoint using either 1.5 or 1.0% tolerance . For all four analyzed outbreaks, PFGE would have given public health officials additional support in declaring an outbreak and making appropriate public health decisions. J Med Microbiol, 2000 Dec, 49(12), 1079 - 84 Investigation for a more virulent variant among the c:2b:P1.2,5 Spanish meningococcal epidemic strains by molecular epidemiology; Arreaza L et al.; A rise in the incidence of meningococcal disease has occurred in Spain in recent years, especially in some regions in the north-west of the country . Most cases have been caused by meningococci characterised as Neisseria meningitidis C:2b:P1.2,5 . A total of 107 C:2b:P1.2,5 meningococcal isolates (60 from patients and 47 from carriers) and 12 isolates showing related antigenic combinations (C:2b:NST, C:2b:P1.2, C:2b:P1.5, C:NT:P1.2,5) was analysed by pulsed-field gel electrophoresis to determine the genetic variability of the epidemic and related strains . Endonucleases BglII and NheI were used to cut chromosomal DNA . When BglII was used, most of the C:2b:P1.2,5 isolates showed the same pulsotype regardless of whether they were from clinical cases or carriers . Isolates showing the principal profile after digestion with endonuclease BglII were analysed with NheI . Four pulsotypes were identified, of which two were found in only one isolate each . The major profiles (1 and 2) showed differential distribution among clinical and carrier isolates; pulsotype 1 was the most frequent among clinical isolates . However, the proportions of isolates showing profiles 1 and 2 were similar among carrier isolates . This could indicate that there are two variants of the C:2b:P1.2,5 strain with differing pathogenicity. J Reconstr Microsurg, 2000 Nov, 16(8), 603 - 7 Limb salvage after fulminant septicemia using a free latissimus dorsi cross-leg flap; Ninkovic MM et al.; A 15-year-old boy survived fulminant meningococcal septicemia, with extensive tissue necrosis involving the face and the right arm, complicated by peripheral gangrene of the fingers on both hands and the distal parts of the feet . Although still often fatal, the mortality of fulminant septicemia has dropped substantially in the past decades, leading to more survivors, and requiring concurrent reconstruction of all extremities . This report discusses the advantages of using a single, free, latissimus dorsi (LD) myocutaneous cross-leg flap to salvage both feet, and the use of pedicled groin flaps bilaterally for coverage of fingers and hands, as illustrated by this case. Nihon Rinsho Meneki Gakkai Kaishi, 1999 Apr, 22(2), 53 - 62 {Clinical findings and genetic bases of congenital complement deficiencies}; Kira R et al.; The clinical findings and genetic bases of inherited deficiencies of plasma complement components and comple