JAMA, 1997 Aug 13, 278(6), 491 - 6 Prognostic factors in meningococcal disease . Development of a bedside predictive model and scoring system . Barcelona Meningococcal Disease Surveillance Group; Barquet N et al.; CONTEXT: Meningococcal disease is associated with significant morbidity and mortality . Development of a prognostic model based on clinical findings may be useful for identification and management of patients with meningococcal infection . OBJECTIVES: To construct and validate a bedside model and scoring system for prognosis in meningococcal disease . DESIGN: Prospective, population-based study . SETTING: Twenty-four hospitals in the metropolitan area of Barcelona, Spain . PATIENTS: A total of 907 patients with microbiologically proven meningococcal disease . Patients diagnosed with meningococcal disease from 1987 through 1990 were used to develop the prognostic model, and those diagnosed in 1991 and 1992 were used to validate it . OUTCOME MEASURES: Clinical independent prognostic factors for mortality in meningococcal disease . The association between outcome and independent prognostic factors was determined by logistic regression analysis . A scoring system was constructed and tested using receiver operating characteristic curves . RESULTS: Among 624 patients in the derivation set, 287 (46%) were male, the mean age was 12.4 years, and 34 patients (5.4%) died . Among 283 patients in the validation set, 124 (43.8%) were male, the mean age was 12.7 years, and 17 patients (6.0%) died . In multivariate analysis, independent predictors of death were hemorrhagic diathesis (odds ratio {OR}, 101; 95% confidence interval {CI}, 30-333), focal neurologic signs (OR, 25; 95% CI, 7-83), and age 60 years or older (OR, 10; 95% CI, 3-34), whereas receipt of adequate antibiotic therapy prior to admission was associated with reduced likelihood of death (OR, 0.09; 95% CI, 0.02-0.4) . Hemorrhagic diathesis was scored with 2 points, presence of focal neurologic signs with 1 point, age of 60 years or older with 1 point, and preadmission antibiotic therapy was scored as -1 . The clinical scores of -1, 0, 1, 2, and 3 or more points were associated with a probability of death of 0%, 2.3%, 27.3%, 73.3%, and 100%, respectively . CONCLUSIONS: Hemorrhagic diathesis, focal neurologic signs, and age of 60 years or older were independent predictors of death in meningococcal disease, whereas receipt of adequate antibiotic therapy was associated with a more favorable prognosis . The scoring system presented is simple, is based on findings readily available at the bedside, and may be useful to help guide aggressive therapy. Commun Dis Intell, 1997 Aug 7, 21(16), 217 - 21 Annual report of the Australian Meningococcal Surveillance Programme 1996; A new classification for pericarditis associated with meningococcal infection; Department of Paediatrics C, Schneider Children's Medical Centre of Israel, Petah TiqvaAcute meningococcal pericarditis is a rare clinical disorder . Our review of the literature disclosed that current classifications are confusing since they fail to differentiate between two distinct criteria: time and causality . We suggest a new classification of the various states of meningococcal pericarditis on the basis of the pathophysiological process: disseminated meningococcal disease with pericarditis (purulent, culture-positive, associated with meningococcal bacteraemia); isolated meningococcal pericarditis (purulent, culture-positive but without signs of meningeal or other clinical systemic involvement); and reactive meningococcal pericarditis (immunological, late-onset, culture-negative, resembling post-viral pericarditis) . It is essential that clinicians recognize the various states of the disease, since they differ in natural history, treatment and prognosis . CONCLUSION: From personal experience and a literature review it emerges that meningococcal pericarditis should be classified as: (1) Pericarditis as local manifestation of disseminated meningococcal disease; (2) isolated meningococcal pericarditis; (3) reactive (immunopathic) meningococcal pericarditis. Microb Pathog, 1997 Aug, 23(2), 71 - 84 Sequence analysis of the structural tbpA gene: protein topology and variable regions within neisserial receptors for transferrin iron acquisition; Pajon R et al.; The gene coding for the 98-kDa meningococcal outer membrane transferrin binding protein 1 (TbpA) from strain B385 was cloned and sequenced . Sequence comparison among its deduced aminoacid sequence and those from TbpA and the closely related LbpA (lactoferrin binding protein) gene from three different meningococcal strains, and four isolates from two other bacterial pathogens, showed that TbpA variability is confined to five specific segments, designated VR1 (199-287), VR2 (306-381), VR3 (480-546), VR4 (618-651) and VR5 (681-708) . The third VR was the most variable among strains both at the nucleotide and amino acid levels . Six additional tbpA genes from different meningococcal strains were cloned and its VR3 sequence determined . On the basis of this data we were able to cluster tbpA genes in two groups: D (bearing a deletion in VR3) and N (nondeleted); all N and D strains belonging to the groups of high or low molecular weight transferrin receptor isotype, respectively . However, by phenogram analysis, the prototypical strain M982 (Group II) was clustered with M990 (B16B6 isotype, Group I) . These results point to the existence of important exposed regions as well as to the possibility of horizontal gene exchange involving this locus . A topology model with 14 exposed loops and 28 membrane spanning segments was postulated . According to this tentative analysis, TbpA as well as LbpA proteins should form a gated channel in the neisserial outer membrane . The variable regions were located in the fifth, sixth, eighth, 10th and 11th loops respectively . Among TbpAs VR1, VR2, and VR3 resulted the most relevant regions. Blood, 1997 Aug 1, 90(3), 1101 - 8 The pattern of interleukin-1beta (IL-1beta) and its modulating agents IL-1 receptor antagonist and IL-1 soluble receptor type II in acute meningococcal infections; van Deuren M et al.; Interleukin-1beta (IL-1beta) is considered an important mediator in the pathogenesis of septic shock or bacterial meningitis . Its activity is specifically modulated by IL-1 receptor antagonist (IL-1Ra) and IL-1 soluble receptor type II (IL-1sRII) . We now describe the time-course of IL-1beta and these modulating agents in 59 patients with acute meningococcal infections, the prototype human disease of acute endotoxin exposure . Plasma IL-1beta was increased only in severe shock and normalized within 12 to 24 hours, indicating that patients were admitted in an early stage of cytokine activation . Increased IL-1beta values in cerebrospinal fluid (CSF) were confined to patients with meningitis . Plasma IL-1Ra was elevated in both shock and nonshock patients, extremely high values being measured in severe shock . High concentrations of IL-1Ra in CSF were found in meningitis . Plasma IL-1Ra peaked shortly after IL-1beta and decreased steeply in 1 to 2 days, followed by sustained moderately elevated levels in shock patients . Interestingly, IL-1sRII showed a completely different pattern . At admission, both nonshock and shock patients manifested a similar moderate increase of plasma IL-1sRII . However, during recovery plasma IL-1sRII further increased reaching maximal concentrations 3 to 5 days after admission, 1 to 2 days after normalization of IL-1Ra . In shock patients this increase was more prominent than in nonshock patients . It is hypothesized that this increase in plasma IL-1sRII can be explained by a synergistic effect of dexamethasone and endotoxin . A second interesting observation was that, unlike the pattern in plasma, IL-1sRII levels in CSF paralleled those of IL-1beta and IL-1Ra . This suggests different modulation of IL-1beta activity in the subarachnoid space and the plasma compartment . We conclude that: (1) During the early stage of meningococcal infections IL-1Ra modulates IL-1 activity, whereas during recovery IL-1sRII may be more important . (2) Modulation in CSF and in the plasma compartment are differentially regulated. Transplantation, 1997 Jul 27, 64(2), 365 - 8 Successful transplantation of organs retrieved from donors with bacterial meningitis; Lopez-Navidad A et al.; BACKGROUND: The shortage of organs for transplantation is the most important factor limiting the number of transplants performed . Consequently, in recent years, criteria for considering a patient as a potential organ donor have been broadened . METHODS: From 1995 through 1996, we have retrieved organs from five donors who were brain dead because of bacterial meningitis . The causative microorganisms were Neisseria meningitidis in one patient, Streptococcus pneumoniae in three patients, and Escherichia coli in one patient . Fifteen organs were retrieved and transplanted into 16 recipients . All the donors and recipients received adequate antibiotic therapy . RESULTS: None of the recipients developed infectious complications caused by the meningeal pathogens . After a follow-up ranging from 4 to 30 months, 12 patients are alive with functioning grafts . The cause of death was noninfectious in the four patients who died . CONCLUSIONS: Our study demonstrates that patients with brain death caused by bacterial meningitis due to meningococci, pneumococci, or E coli may be suitable organ donors . Transplantation of organs from such donors does not increase the risk of infection transmission to the recipient, provided that both donor and recipient had received adequate antibiotic therapy. Vaccine, 1997 Jul, 15(10), 1144 - 8 A randomized, placebo-controlled study of oral cimetidine as an immunopotentiator of parenteral immunization with a group B meningococcal vaccine; Drabick JJ et al.; Cimetidine (CIM) is an H2-receptor antagonist with a long history of clinical use in peptic ulcer disease . In addition to its inhibitory effect upon gastric acid secretion, CIM can also block histamine-mediated immunosuppression by inhibiting H2 receptors on suppressor T cells . CIM results in immunoaugmentation of both cellular and humoral immunity by this mechanism and has been used clinically in the treatment of chronic infectious and neoplastic diseases . We postulated that orally administered CIM, like an adjuvant, could augment the immunologic response to a parenteral vaccine . To test this hypothesis, a randomized placebo (PLB)-controlled, double-blinded study in 14 healthy volunteers was performed using a Group B meningococcal outer membrane protein (OMP) vaccine administered twice, 6 weeks apart . Volunteers were randomized within pairs defined by their screening OMP antibody titers to receive either CIM or PLB which was administered for 5 days, beginning 2 days before each of the two immunizations . All 14 volunteers completed the study with excellent compliance . Sera were tested for anti-OMP and bactericidal antibodies . The groups were comparable in terms of gender distribution, age and baseline anti-OMP titers . Reactogenicity to the vaccine was mild and comparable between groups . There was little effect of CIM (over PLB) on anti-OMP or functional bactericidal antibody levels over time . Geometric means of maximum OMP antibody increase over baseline was 3.3-fold (95% CI: 1.8-6.3) for CIM and 2.4 for PLB (CI: 1.6-3.7) . CIM had a corresponding 3.9-fold increase (CI: 1.9-8.3) in bactericidal antibody level compared to 2.2 for PLB (CI: 1.4-3.4) . We conclude that oral CIM was not effective as an immunopotentiator of immunization with this group B meningococcal vaccine. Am J Orthop, 1997 Jul, 26(7), 491 - 3 Reconstruction of the heel pad in ankle disarticulation with a free muscle transfer; Pinzur MS et al.; An otherwise healthy 17-year-old young man developed bilateral heel pad necrosis due to meningococcemia, adult respiratory distress syndrome, and disseminated intravascular coagulation . Bilateral ankle disarticulation amputations were salvaged by use of a dorsally based local flap on one residual limb and a free muscle transfer to reconstruct the weight-bearing surface of the contralateral residual limb . The case report illustrates two methods of unusual salvage of the end-bearing, weight-bearing surface of the residual limbs in a bilateral end-bearing amputation. Infect Immun, 1997 Jul, 65(7), 2613 - 20 Characterization of a class II pilin expression locus from Neisseria meningitidis: evidence for increased diversity among pilin genes in pathogenic Neisseria species; Aho EL et al.; Strains of Neisseria meningitidis elaborate one of two classes of pili . Meningococcal class I pili have many features in common with pili produced by N . gonorrhoeae, including the ability to bind monoclonal antibody SM1 and a common gene and protein structure consisting of conserved, semivariable, and hypervariable regions . Class II pili are SM1 nonreactive and display smaller subunit molecular weights than do gonococcal or meningococcal class I pili . In this study, we have determined the N-terminal amino acid sequence for class II pilin and isolated the expression locus encoding class II pilin from N . meningitidis FAM18 . Meningococcal class II pilin displays features typical of type IV pili and shares extensive amino acid identity with the N-terminal conserved regions of other neisserial pilin proteins . However, the deduced class II pilin sequence displays several unique features compared with previously reported meningococcal class I and gonococcal pilin sequences . Class II pilin lacks several conserved peptide regions found within the semivariable and hypervariable regions of other neisserial pilins and displays a large deletion in a hypervariable region of the protein believed to be exposed on the pilus face in gonococcal pili . DNA sequence comparisons within all three regions of the coding sequence also suggest that the meningococcal class II pilin gene is the most dissimilar of the three types of neisserial pilE loci . Additionally, the class II locus fails to display flanking-sequence homology to class I and gonococcal genes and lacks a downstream Sma/Cla repeat sequence, a feature present in all other neisserial pilin genes examined to date . These data indicate meningococcal class II pili represent a structurally distinct class of pili and suggest that relationships among pilin genes in pathogenic Neisseria do not necessarily follow species boundaries. J Clin Microbiol, 1997 Jul, 35(7), 1809 - 12 PCR-single-stranded confirmational polymorphism analysis for non-culture-based subtyping of meningococcal strains in clinical specimens; Newcombe J et al.; Subspecific typing of clinical meningococcal strains is important in the investigation of outbreaks and for disease surveillance . Serogrouping, typing, and subtyping of strains currently require isolation of a meningococcus from one or more clinical specimens . However, the increasing widespread practice of preadmission administration of parenteral antibiotics has resulted in a decrease in the frequency of positive cultures obtained from blood and cerebrospinal fluid . Confirmation of meningococcal disease can be obtained by meningococcus-specific PCR from both cerebrospinal fluid (H . Ni et al., Lancet 340:1432-1434, 1992) and peripheral blood (J . Newcombe et al., J . Clin . Microbiol . 34:1637-1640, 1996) specimens . However, current PCR protocols do not yield epidemiologically useful typing information . We report here the use of PCR-single-stranded confirmational polymorphism (PCR-SSCP) analysis to amplify and type meningococcal DNA present in clinical specimens . PCR-SSCP analysis with the VR1 region of the Neisseria meningitidis porA gene as the target produced unique banding patterns for each serosubtype . Direct PCR-SSCP of clinical specimens can therefore provide typing data that can be used to investigate the epidemiology of clusters of cases and outbreaks and for disease surveillance in situations in which culture of patient specimens proves negative. Clin Immunol Immunopathol, 1997 Jul, 84(1), 27 - 35 Vaccine-induced IgG antibodies to the linear epitope on the PorB outer membrane protein promote opsonophagocytosis of Neisseria meningitidis by human neutrophils; Delvig AA et al.; The serotype 15 PorB protein of Neisseria meningitidis contains an N-terminal linear immunodominant B-cell epitope located on the putative loop 1 (VR1) region . This epitope has previously been shown to stimulate antibody formation in 74% of the vaccinees after three doses of the Norwegian group B outer-membrane vesicle (OMV) vaccine . In the present study, the purified PorB protein and the 23mer synthetic peptide D63b2 covering VR1 region were immobilized onto N-hydroxysuccinimide-activated matrix and used for affinity purification of the specific IgG antibodies from sera of three selected vaccinees . PorB- and peptide D63b2-specific IgG preparations bound to the PorB protein on immunoblots and reacted with strain 44/76 and OMV complexes expressing the serotype 15 PorB protein, but not with the PorB-deficient mutant, suggesting high specificity for the PorB protein . Both PorB- and peptide D63b2-specific IgG were marginally bactericidal, but enabled strong opsonophagocytosis measured as respiratory burst response of human neutrophils and internalization of opsonized FTTC-labeled meningococci . The data indicate that about 30-57% of the bulk serum opsonic activity for the 44/76 bacteria could be ascribed to linear epitope-specific IgG1, thus contributing to vaccine-induced protection against systemic meningococcal disease via the opsonophagocytic route of pathogen clearance. Gene, 1997 Jun 11, 192(1), 155 - 63 The pilus colonization factor of pathogenic neisserial species: organelle biogenesis and structure/function relationships--a review; Tonjum T et al.; Type-IV pilus expression plays a critical role in the interactions between Neisseria gonorrhoeae, Neisseria meningitidis and their human host . We have focused on experiments designed to elucidate the mechanisms of organelle biogenesis as one means of understanding the complexities of pilus biology in these species . Employing a variety of approaches, genes and gene products essential to pilus biogenesis have been identified and characterized . The findings indicate that the neisserial type-IV pilus biogenesis machinery is most closely related to that operating in Pseudomonas aeruginosa and other pseudomonad species . This interrelatedness is documented at the levels of gene organization, DNA homologies and identities between the primary structures of the components . Despite these similarities, the biological correlates of pilus expression in the pathogenic Neisseria are quite unique . The current status of our embryonic understanding of the factors influencing organelle biogenesis is presented . In the context of this workshop, emphasis has been placed on specific contributions made through studies of gonococci and meningococci to the field as a whole.. Gene, 1997 Jun 11, 192(1), 149 - 53 Type-4 pili and meningococcal adhesiveness; Nassif X et al.; The ability to interact with non-phagocytic cells is a crucial virulence attribute of the meningococcus . Pili play a major role in this process and are the only means yet discovered by which capsulated bacteria may adhere to cells . Pilus-mediated adhesion is a two-step process which requires (i) the expression of the adhesin PilC1 and (ii) the expression of an appropriate pilin variant . Some pilin variants have the ability to modify the degree of adhesiveness through the formation of bundles of pili which increases bacteria-bacteria interactions. Gene, 1997 Jun 11, 192(1), 141 - 7 Post-translational modifications of meningococcal pili . Identification of common substituents: glycans and alpha-glycerophosphate--a review; Virji M; Neisseria meningitidis elaborate filamentous adhesins, pili or fimbriae, which belong to the type-4 structural group of pili also found on other bacterial pathogens such as Neisseria gonorrhoeae, Pseudomonas aeruginosa, Moraxella bovis and Dichelobacter nodosus . Meningococcal pili readily undergo structural variations which arise as a result of inter- and intra-genomic recombinational events . Structural variations often result in variations in bacterial adhesion mediated by pili . Studies on structure/function relationship of meningococcal pili have shown that pili are post-translationally modified and contain unusual covalently-linked substituents . The presence of glycans was shown by the use of specific carbohydrate labelling, chemical deglycosylation and by introducing galE mutations; the latter studies confirmed the presence of galactose on pili . Mass spectrometric and other analysis of pilin-derived tryptic peptides and linked substituents were used to determine the structure of an unusual O-linked trisaccharide, Gal beta1-4 Gal alpha1-3{2,4-diacetamido-2,4,6-trideoxyhexose} . Similar studies have also identified, perhaps a unique substituent, alpha-glycerophosphate, which is attached to Ser93 by a phosphodiester linkage. Med J Aust, 1997 Jun 2, 166(11), 598 - 601 New guidelines for management and prevention of meningococcal disease in Australia . Meningococcal Disease Working Party of the National Health and Medical Research Council; Patel MS et al.; The incidence of invasive meningococcal disease in Australia has increased over the past decade, and in April 1997 the National Health and Medical Research Council published guidelines for management of patients with meningococcal disease and their contacts . These guidelines emphasise the need for immediate intravenous antibiotic treatment of patients with suspected meningococcal disease, before transfer to hospital or lumbar puncture . When possible, blood for culture should be collected before antibiotic therapy, if this does not delay treatment. J Exp Med, 1997 Jun 2, 185(11), 1929 - 38 N-Propionylated group B meningococcal polysaccharide mimics a unique bactericidal capsular epitope in group B Neisseria meningitidis; Pon RA et al.; The N-propionylated group B meningococcal polysaccharide (NPrGBMP) mimics a unique protective epitope on the surface of group B meningococci (GBM) and Escherichia coli K1 . Using a series of monoclonal antibodies (mAbs) induced by the NPrGBMP-monomeric tetanus toxoid (TT) conjugate vaccine it was demonstrated that mAbs having specificities for both extended and conventional short segments of the NPrGBMP were formed, but only the former were bactericidal, and/or gave passive protection against live challenge by GBM . The failure of mAbs specific for short epitopes to protect was further established when (NeuPr)4-TT was used as the vaccine . Of all the mAbs produced that were specific for short internal segments of the NPrGBMP, none were protective, despite the fact that most of them cross-react with the GBM capsular polysaccharide . In contrast, most of the protective mAbs produced by NPrGBMP- TT did not recognize the group B meningococcal polysaccharide (GBMP) unless it was present in its aggregated high molecular weight form . The bactericidal epitope mimicked by the NPrGBMP was shown to be ubiquitous in the capsule of both GBM and E . coli K1 using immunogold labeling techniques and, because of its unique properties, its identification could be significant in the development of a comprehensive conjugate vaccine against group B meningococcal meningitis . This is because most known human alpha(2-8)-polysialic acid self-antigens can be accommodated in 30-50 alpha(2-8)-linked sialic acid residues, which is roughly equivalent to an 11-kD length of the GBMP . It has been hypothesized that the formation of the protective epitope on the surface of GBM is due to the interaction of helical segments of the GBMP with another molecule and that the protective epitope is mimicked by the NPrGBMP . Support for the above hypothesis is provided by the fact that the protective NPrGBMP epitope has a similar unusual length dependency to that of the GBMP epitope. J Public Health Med, 1997 Jun, 19(2), 162 - 70 Community immunization programme in response to an outbreak of invasive Neisseria meningitidis serogroup C infection in the Trent region of England 1995-1996; Irwin DJ et al.; Between 8 December 1995 and 16 January 1996 seven laboratory confirmed cases of septicaemia owing to infection with Neisseria meningitidis serogroup C strains and one highly probable case of meningococcal septicaemia occurred in three electoral wards in south Rotherham and the Retford area of north Nottinghamshire . All cases occurred among children aged 1-17 years . One patient died . The public health response to this outbreak was the largest community prophylactic antibiotic and immunization programme against meningococcal infection, to date, in the United Kingdom . The target group for each Health Authority was 8900 for Rotherham Health Authorities and 8000 for North Nottinghamshire Health . Local logistical factors led to differences in the implementation of the programme by each Health Authority . At the completion of each programme, 8320 doses of vaccine had been administered (92.5 per cent coverage) during the Rotherham Health Authorities programme and 7660 (95.7 per cent coverage) during the North Nottinghamshire Health programme . The additional financial cost of the exercise amounted to approximately Pounds 125000 for each Health Authority . This paper describes the evolution of the outbreak, the decision-making process resulting in the immunization programme in each Health Authority, the implementation of each programme, problems identified and lessons learned. J Hand Surg {Br}, 1997 Jun, 22(3), 408 - 10 Peripheral gangrene associated with fulminating meningococcal septicaemia . Is early escharotomy indicated? Fitton AR, Dickson WA, Shortland G, Smithies M. We present a case of a 3-month-old boy presenting with fulminating meningococcal septicaemia associated with extensive peripheral gangrene requiring amputation of three limbs . The surgical management options and the role of early fasciotomy are discussed. J Formos Med Assoc, 1997 Jun, 96(6), 461 - 4 Mixed meningococcal and tuberculous meningitis; Yeh TH et al.; Meningococcal meningitis is one of the most common bacterial infections of the meninges worldwide, and tuberculous infection is the most common cause of chronic meningitis in Taiwan . However, mixed meningococcal and tuberculous meningitis is rare . We describe a 27-year-old woman with a case of culture-proven meningococcal and tuberculous meningitis verified by polymerase chain reaction on a cerebrospinal fluid specimen . The patient was initially treated with intravenous antibiotics including penicillin G and chloramphenicol . Though the patient responded well to therapy initially, her subsequent clinical deterioration was finally controlled by long-term antituberculous medications. Eur J Pediatr, 1997 Jun, 156(6), 451 - 3 Plasma fibronectin levels in meningococcal disease; Riordan FA et al.; Fibronectin (a glycoprotein which modulates inflammation) may decrease mortality in systemic infection . Children with meningococcal disease (MCD) may have low fibronectin levels . We aimed to compare plasma fibronectin levels in children with MCD and controls, correlate fibronectin levels with interleukin-6 (IL-6), shock and death, and assess fibronectin as an aid to early diagnosis in MCD . Samples were taken on admission from 99 children with MCD and 49 controls . Plasma fibronectin was measured using a turbidimetric immunoassay . Plasma fibronectin was significantly lower in MCD compared to controls (57 micrograms/ml vs 105 micrograms/ml; P < 0.005) . Children who died had significantly lower levels than survivors (29 micrograms/ml vs 62 micrograms/ml; P = 0.01) . Fibronectin levels were negatively correlated with IL-6 levels . Fibronectin was a poor predictor of MCD . CONCLUSION: Plasma fibronectin levels are decreased in children with MCD, especially in shock and death . This decrease is associated with high IL-6 levels . Fibronectin could be a novel therapy in severe MCD. Crit Care Med, 1997 Jun, 25(6), 1079 - 82 Recombinant tissue plasminogen activator restores perfusion in meningococcal purpura fulminans; Aiuto LT et al.; OBJECTIVE: To investigate whether an infusion of recombinant tissue plasminogen activator would dissolve microvascular thromboses and improve organ perfusion in a patient with fulminant meningococcemia . DESIGN: Descriptive case report . SETTING: Fifteen-bed pediatric intensive care unit (ICU) in a university hospital . PATIENT: A 4-month-old male with fulminant meningococcemia, refractory shock, and multiple organ failure . INTERVENTIONS: In addition to standard aggressive ICU care, the patient received a recombinant tissue plasminogen activator infusion at a total dose of 1.25 mg/kg over 4 hrs . MEASUREMENTS AND MAIN RESULTS: Heart rate, arterial blood pressure, urine output, and base deficit (as a reflection of severity of metabolic acidosis) were recorded immediately before the recombinant tissue plasminogen activator infusion and 4 hrs later, after completion of the recombinant tissue plasminogen activator infusion . The amount of exogenous vasopressor and inotropic support required to maintain the patient's hemodynamic status before and after recombinant tissue plasminogen activator infusion were also compared . Subjective observations regarding the patient's peripheral perfusion status were also noted . The patient showed a dramatic improvement in hemodynamics, urine output, and metabolic acidosis, as well as a perceived increase in skin perfusion after recombinant tissue plasminogen activator infusion . CONCLUSIONS: In this patient, recombinant tissue plasminogen activator infusion resulted in improved organ perfusion and cardiac performance . Selective use of recombinant tissue plasminogen activator in the treatment of fulminant meningococcemia merits further investigation. FEMS Microbiol Lett, 1997 Jun 1, 151(1), 41 - 9 Cloning and characterization of the Neisseria meningitidis rfaC gene encoding alpha-1,5 heptosyltransferase I; Stojiljkovic I et al.; We cloned and characterized the Neisseria meningitidis rfaC gene which encodes an enzyme, alpha-1,5 heptosyltransferase I, involved in the synthesis of the deep-core of the lipooligosaccharide . The N . meningitidis rfaC mutant, obtained by an allelic exchange, produced lipooligosaccharide which migrated faster in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the lipooligosaccharide isolated from the wild-type N . meningitidis . The N . meningitidis rfaC mutant was not affected by growth in a rich microbiological medium and did not show any defect in adhesion to epithelial cell lines . Conversely, the rfaC mutant was attenuated in the infant rat model of meningococcemia, thus confirming the importance of intact lipooligosaccharide in the virulence of N . meningitidis. Clin Exp Immunol, 1997 Jun, 108(3), 497 - 9 Heterozygous C8beta complement deficiency does not predispose to meningococcal disease; Platonov AE et al.; We have identified 42 Russian patients with homozygous C8beta complement component deficiency, all of whom had experienced at least one episode of systemic meningococcal disease . About 90% of these individuals have a C --> T exchange in exon 9, leading to a premature stop codon . If, like the homozygous-deficient state, heterozygous C8beta deficiency constitutes a risk factor for meningococcal disease, it would be expected to be detected with increased frequency among individuals suffering from this disease . Using allele-specific polymerase chain reaction (PCR), we studied 153 consecutive patients with meningococcal disease admitted to the Moscow Hospital for Infectious Diseases to determine the frequency of C8 null allele . No individuals with heterozygous C --> T exchange were identified among these 153 patients, despite the fact that seven persons were detected who had homozygous C8beta deficiency, caused by the same C --> T exchange in exon 9, and one patient who had C7 component deficiency . Thus, heterozygous deficiency, although more frequent than homozygous deficiency in the general population, does not result in a substantial increase in susceptibility to meningococcal disease. Cas Lek Cesk, 1997 May 7, 136(9), 286 - 8 {Treatment of meningococcal sepsis}; Kasal E et al.; BACKGROUNDS: Incidence of meningococcal diseases and sepsis caused by a new invasive strain of Neisseria meningitidis group C: 2a: P 1,2 has been observed in the Czech republic within the last 3 years . In 1994 the highest incidence of this disease was in the West region . Ten of the most critically ill patients were treated at the Department of Anaesthesiology and Intensive Care . The aim of this work was to present principles of the treatment of this disease . METHODS AND RESULTS: In 1994 we treated 10 patients, 8 male and 2 female with average age of 11 years (range from 5 months to 20 years) . Causing strain identification was done in 9 patients, in one patient causing strain was not identified . All patients had typical clinical symptoms of the disease . All of them were treated according to the same protocol of the invasive complex treatment including artificial ventilation, circulation support, Ceftriaxon combined with potassium salt of benzylpenicillin, i.v . immunoglobulins, fresh frozen plasma, heparin, fibrinogen and antitrombin III . Average length of the stay in the Intensive Care Unit was 5 days (range from 1.5 hour to 10 days) . Survival in our group was 70% . CONCLUSIONS: Early started complex therapy is a decisive factor of its success . A uniform protocol of treatment and its wide publication even to the first contact level can increase a chance for survival. Gene, 1997 May 6, 190(2), 263 - 70 Isolation and characterization of the Neisseria meningitidis lpxD-fabZ-lpxA gene cluster involved in lipid A biosynthesis; Steeghs L et al.; The lpxD-fabZ-lpxA gene cluster involved in lipid A biosynthesis in Neisseria meningitidis has been cloned and sequenced . By complementation of a temperature-sensitive E . coli lpxD mutant, we first cloned a meningococcal chromosomal fragment that carries the lpxD homologue . Cloning and sequence analysis of chromosomal DNA downstream of lpxD revealed the presence of the fabZ and lpxA genes . This gene cluster shows high homology to the corresponding genes from several other bacterial species . The LpxA and LpxD proteins catalyze early steps in the lipid A biosynthetic pathway, adding the O- and N-linked 3-OH fatty acyl chains, respectively . In E . coli and N . meningitidis, LpxD has the same specificity, in both cases adding 3-OH myristoyl chains; in contrast to E . coli, the meningococcal LpxA protein is presumed to add 3-OH lauroyl chains instead . The established sequence points the way to further experiments to define the basis for this difference in specificity, and should allow modification of meningococcal lipid A biosynthesis through gene exchange. Aust N Z J Ophthalmol, 1997 May, 25(2), 167 - 8 Meningococcal conjunctivitis; Irani F et al.; BACKGROUND: Primary meningococcal conjunctivitis is a rare condition that can have devastating ocular and systemic complications . METHODS: Review of the case records . CONCLUSIONS: Appropriate Gram stain and cultures should be obtained in cases of hyperacute conjunctivitis, especially in young patients, and systemic antibiotics should be initiated promptly where Gram-negative diplococci are found and prophylaxis for close contacts considered in Neisseria meningitidis conjunctivitis. Trop Med Int Health, 1997 May, 2(5), 433 - 9 {Evaluation of the completeness of the epidemiological surveillance systems for malaria by the Capture-recapture system in the French armies in l994}; Deparis X et al.; The Capture-recapture method has been utilized to evaluate the annual incidence of malaria in the French armies in 1994 on the basis of the incidence derived from two regulatory systems, passive and exhaustive, of epidemiological surveillance: the Recueil et l'Exploitation des Donnees Epidemiologiques des Armees (REDEA) and the Surveillance Epidemiologique du Paladisme (SESP) system . Cases of malaria found by REDEA and SESP in 1994 rose to 480 and 424 respectively . Two hundred and thirty-eight cases were found by both systems . After validating the conditions for the application of the Capture-recapture method (in particular, having verified that the results from REDEA and SESP were probably independent), its utilization allowed us to evaluate the incidence of malaria in the French army in 1994 at 854 cases . The calculated exhaustivity values for REDEA and SESP were 56.2 and 49.6% respectively; 22% of cases were missed by both systems . The exhaustivity values of SESP and REDEA estimated in our study were comparable to those obtained by the Capture-recapture method applied in another legal inquiry into the passive and exhaustive epidemiological surveillance of meningitis and meningococcosis in France in 1989 and 1990 . These results show that it is difficult to evaluate the epidemiological importance of a sickness on the results of passive and exhaustive surveillance alone . In 1995, a new system of surveillance was established in the army: a better conducted and more motivated retro-informative system, linked to a better education of medical officers in epidemiological surveillance permitted an improvement in the completeness of the results in the armies. Pathology, 1997 May, 29(2), 201 - 5 Typing of Neisseria meningitidis by restriction analysis of the amplified porA gene; Speers DJ et al.; We tested a typing system for 54 isolates of Neisseria meningitidis using polymerase chain reaction (PCR) amplification of the porA gene . The isolates were obtained between 1989 and 1994 from cases in Western Australia and Sydney . The PCR product was digested by five restriction endonucleases (AluI, HaeIII, HinfI, RsaI and HpaII) giving a restriction fragment length polymorphism (RFLP) pattern for each isolate . All of the isolates were able to be assigned an RFLP pattern, whereas 24 could be fully serotyped and serosubtyped . The method was rapid and simple to perform and results were easy to interpret . Two outbreaks of invasive meningococcal disease were included in the analysis, one involving an hyperendemic focus of disease and the other characteristic of a point outbreak . The typing system demonstrated the genetic relatedness of isolates from the point outbreak and the genetic diversity among the hyperendemic strains . We conclude that the method is discriminatory and is a useful supplement to serological typing for studying Australian outbreaks of invasive meningococcal disease. J Infect, 1997 May, 34(3), 227 - 35 Acute meningococcal meningitis: analysis of features of the disease according to the age of 255 patients . Copenhagen Meningitis Study Group; Andersen J et al.; Clinical and laboratory features of acute meningococcal meningitis according to age were studied in 255 patients . Whereas males accounted for three out of five patients aged 0-4 years, females accounted for three out of four patients older than 50 years of age . All patients had clinical signs of nuchal rigidity and fever . Patients older than 30 years of age had less frequent petechiae (62%) than younger patients (81%) . Furthermore, elderly patients above 50 years of age were prone to an obtunded mental state and a prolonged disease course with fever . Without relation to age, 2/3 had purulent meningitis and 2/3 had marked peripheral leucocytosis (> 15 x 10(9) cells/l); 90% of patients had at least one of these findings . The cellular inflammatory response in peripheral blood indicated a bacterial aetiology in > 95% of the cases . More than 80% of children and adults had abnormal CSF biochemical findings, but the level of protein and the glucose ratio (CSF/serum) were positively and negatively correlated to increasing age of the patient, respectively: thus, in children these biochemical markers may be unreliable in the differentiation between a bacterial and non-bacterial aetiology . Thrombocytopenia (< 100.000 x 10(9)/I) was not associated with age, though the lowest platelet count was found in elderly patients . The case fatality rate was 7.5%, but neither age, sex nor sign of septicaemia was associated with fatality . Thrombocytopenia, a lowered coagulation index (< 0.5, factors II, VII, X), a moderate anaemia (haemoglobin < 11 g/dl), an obtunded mental state and a history of convulsions were poor prognostic factors; only anaemia was independently correlated to fatality so this should be considered as an important prognostic marker in the acute phase of meningococcal meningitis. Anal Biochem, 1997 May 1, 247(2), 382 - 8 On the interaction between a bactericidal antibody and a PorA epitope of Neisseria meningitidis in outer membrane vesicles: a competitive fluorescence polarization immunoassay; van den Elsen JM et al.; This paper describes a method for determining the affinity constant (Ka) of the binding between an antibody Fab fragment and a membrane-embedded protein epitope under equilibrium conditions . Monoclonal antibody MN12H2, directed against outer membrane protein PorA of Neisseria meningitidis, is used in a competitive fluorescence polarization assay with a cyclic peptide-fluorescein conjugate as a tracer antigen . Displacement experiments with PorA-containing and PorA-deficient meningococcal outer membrane vesicles revealed highly specific binding of MN12H2 Fab to the membrane-embedded PorA P1.16 epitope with Ka of 1.5 x 10(8) M-1. Microb Pathog, 1997 May, 22(5), 295 - 304 Phenotypic variants of meningococci and their potential in phagocytic interactions: the influence of opacity proteins, pili, PilC and surface sialic acids; McNeil G et al.; In previous studies we have examined the roles of meningococcal surface structures (capsule, lipopolysaccharides, pili and opacity proteins: Opa and Opc) in bacterial interactions with human epithelial, endothelial and mononuclear phagocytic cells . In the current investigations, using defined derivatives of a serogroup A strain C751 and a serogroup B strain MC58, we studied the roles of these structures with human polymorphonuclear phagocytes (PMN) . In addition, we examined the potential influence of the pilus-associated protein, PilC, previously known to affect epithelial cell interactions . The data show, that, as with monocytes, opacity proteins affect bacterial interactions with PMN and require surface sialic acids (on capsule and LPS) to be down-modulated in order to function . Also, in contrast to their role in human epithelial and endothelial adherence, neither pili nor PilC expression had any effect on phagocytic cell interactions with respect to induction of chemiluminescence as well as phagocytic killing . Examination of the relative influence of Opa and Opc indicated that Opa proteins are more effective than Opc in PMN interactions whereas the reverse was the case with monocytes . These results suggest that Opa and Opc mediate interactions with phagocytic cells via distinct mechanisms . Observations presented here and reported previously collectively show that the structural requirements of meningococci for interacting with phagocytes, in the absence of opsonins, are present in the phenotype which is often isolated from the nasopharynx (asialylated, piliated, Opa/Opc+) whereas the phenotype prevalent in the blood (sialyted, piliated, Opa/Opc+) retains the ability to adhere to endothelial cells (via pili) but appears to be refractory to interactions with phagocytic cells. Clin Diagn Lab Immunol, 1997 May, 4(3), 345 - 51 Measurement of antibodies against meningococcal capsular polysaccharides B and C in enzyme-linked immunosorbent assays: towards an improved surveillance of meningococcal disease; Andersen J et al.; In order to improve the surveillance of serogroup B and C meningococcal diseases, enzyme-linked immunosorbent assays (ELISAs) specific for anti-B immunoglobulin M (IgM) and anti-C IgM and IgG antibodies were developed . The tests were evaluated by using paired sera from 122 patients with and 101 patients without laboratory evidence of meningococcal disease . Fifty-three of 67 patients (79%) with culture-confirmed serogroup B disease had an anti-B IgM antibody response; anti-B IgM levels waned rapidly in children < or = 4 years of age . Twenty-four of 25 patients (96%) with culture-confirmed serogroup C disease had an anti-C IgM and/or IgG antibody response (IgM, 92%; IgG, 68%) . In patients without evidence of meningococcal disease, 19% of children < or = 4 years of age and 69% of those > 4 years of age had intermediate anti-B IgM titers . In contrast, only 1 and 5% of these patients had intermediate titers of anti-C IgM and anti-C IgG, respectively . The ELISAs were shown to be powerful tools for discriminating between serogroup B and C diseases in 96 to 100% of culture-confirmed cases . For 90% of patients with culture-negative meningococcal disease, a serogroup-specific diagnosis could be established by examination of paired sera in the ELISAs . As serogroup B and C meningococci account for practically all cases of meningococcal disease in industrialized countries, the availability of these tests may improve surveillance and prevention. Infect Immun, 1997 May, 65(5), 1972 - 9 Modulation of the biological activities of meningococcal endotoxins by association with outer membrane proteins is not inevitably linked to toxicity; Quakyi EK et al.; Meningococcal sepsis results partly from overproduction of host cytokines after macrophages interact with endotoxin . To obtain less toxic and highly immunomodulatory meningococcal endotoxins for prophylactic purposes, we investigated the relationship between endotoxicity and immunomodulatory activity of several endotoxin preparations from Neisseria meningitidis group B . Using the D-galactosamine-sensitized mouse model to determine endotoxin lethality, we found that the toxicity of purified lipooligosaccharide (LOS) from M986, a group B disease strain, was three to four times higher than those of purified LOSs from the noncapsulated strains M986-NCV-1 and OP-, the truncated-LOS mutant . The LOSs of outer membrane vesicles (OMVs) and detergent-treated OMVs (D-OMVs) from the three strains were 2 to 3 and over 300 times less toxic than the purified LOSs, respectively . Intraperitoneal administration of these preparations induced production of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in serum 2 h after injections . However, repeated doses of low- and high-toxicity preparations induced lower amounts of TNF-alpha and IL-6, i.e., LOS tolerance . Injection of mice with low doses of LOS was as effective as injection with high doses in inducing tolerance . Peritoneal macrophages from tolerant mice pretreated with either high- or low-toxicity LOS preparations produced only a fraction of the amounts of TNF-alpha and IL-6 produced by control groups in response to LOS ex vivo . Despite tolerance to LOS induced by pretreatment with reduced-toxicity preparations, killing of N . meningitidis M986 by macrophages from these animals was enhanced . Protection was achieved when mice treated with LOS, and especially that of D-OMVs, were challenged with live N . meningitidis . The least toxic LOS, that in D-OMVs, was most effective in inducing hyporesponsiveness to endotoxin in mice but protected them against challenge with N . meningitidis . No inevitable link between toxicity and host immune modulation and responses was shown . Our results show that LOS is responsible for both toxicity and immunomodulation . When LOS is tightly associated with outer membrane proteins in D-OMV, it reduces toxicity but enhances beneficial effects compared to results with its purified form . Thus, systematic and critical evaluation of D-OMVs as adjuvants or as portions of group B meningococcal vaccines may help improve survival and outcome in meningococcal sepsis. J Biol Chem, 1997 Apr 18, 272(16), 10710 - 20 Structural and functional characterization of a recombinant PorB class 2 protein from Neisseria meningitidis . Conformational stability and porin activity; Minetti CA et al.; An outer membrane PorB class 2 protein from Neisseria meningitidis has been overexpressed in Escherichia coli, isolated from inclusion bodies, and refolded in the presence of zwitterionic detergent . The purified recombinant and native (strain M986) counterpart exhibit most of the typical functional and structural properties that are characteristic of bacterial porins . Channel forming activity has been monitored by incorporating class 2 into reconstituted liposomes and measuring the permeation rates of various oligosaccharides through the proteoliposomes to derive a pore diameter of approximately 1.6 nm . Structural studies employing a combination of spectroscopic and electrophoretic techniques reveal that recombinant and native class 2 are identical in terms of overall conformational stability . Both proteins form stable trimers in zwitterionic detergent and retain significant secondary and tertiary structure in the presence of SDS . The thermal unfolding of zwittergen-solubilized class 2 trimers (Tm = 88 degrees C) is reversible and characterized by solvent exposure of aromatic residues with concomitant disruption of tertiary and partial loss of secondary structures . SDS-induced destabilization and irreversible unfolding of the native trimeric assembly occurs at temperatures above 60 degrees C . Our physicochemical studies of PorB class 2 protein furnish significant insight regarding the structural and functional properties of this meningococcal outer membrane protein within the porin superfamily. J Exp Med, 1997 Apr 7, 185(7), 1173 - 83 Highly conserved Neisseria meningitidis surface protein confers protection against experimental infection; Martin D et al.; A new surface protein, named NspA, which is distinct from the previously described Neisseria meningitidis outer membrane proteins was identified . An NspA-specific mAb, named Me-1, reacted with 99% of the meningococcal strains tested indicating that the epitope recognized by this particular mAb is widely distributed and highly conserved . Western immunoblotting experiments indicated that mAb Me-1 is directed against a protein band with an approximate molecular mass of 22,000, but also recognized a minor protein band with an approximate molecular mass of 18,000 . This mAb exhibited bactericidal activity against four meningococcal strains, two isolates of serogroup B, and one isolate from each serogroup A and C, and passively protected mice against an experimental infection . To further characterize the NspA protein and to evaluate the protective potential of recombinant NspA protein, the nspA gene was identified and cloned into a low copy expression vector . Nucleotide sequencing of the meningococcal insert revealed an ORF of 525 nucleotides coding for a polypeptide of 174 amino acid residues, with a predicted molecular weight of 18,404 and a isoelectric point of 9.93 . Three injections of either 10 or 20 microg of the affinity-purified recombinant NspA protein efficiently protected 80% of the mice against a meningococcal deadly challenge comparatively to the 20% observed in the control groups . The fact that the NspA protein can elicit the production of bactericidal and protective antibodies emphasize its potential as a vaccine candidate. Commun Dis Rep CDR Rev, 1997 Apr 4, 7(4), R55 - 9 Meningococcal disease in England and Wales: 1995; Kaczmarski EB; The number of laboratory confirmed cases of meningococcal infection in England and Wales rose in 1995 for the first time since 1990 . Culture confirmed cases rose to 1459, an increase of 29% over the 1994 total, due largely to increased disease activity in the last quarter of 1995 . Cases diagnosed by non-culture methods totalled 431, giving a total of 1890 laboratory confirmed cases . Notifications reported to the Office of Population Censuses and Surveys also increased to a similar extent . Northern regions generally had higher rates of disease activity and greater increases in rates . Meningococcal disease caused by serogroup C strains accounted for the main increase in culture confirmed cases and made up 32% of the total in 1995 . Disease caused by C2a strains showed a particularly large increase . A change in the age distribution was noted with a greater proportion of patients in older age groups . Among group B isolates, B4 P1.4 strains continued to be identified most commonly. Commun Dis Rep CDR Rev, 1997 Apr 4, 7(4), R49 - 54 Changing patterns of case ascertainment and trends in meningococcal disease in England and Wales; Ramsay M et al.; We have reviewed data on meningococcal disease routinely collected in England and Wales from 1989 to 1995 to illustrate and explain changing patterns and guide future surveillance . Statutory notifications of meningococcal meningitis and septicaemia, laboratory confirmed infections, and death registrations coded as meningococcal disease were analysed in terms of their numbers, the age of cases, season of the report, and (if available) site of isolation, serogroup, and serotype . Case fatality rates were estimated for clinically diagnosed and culture confirmed cases . The number of cases notified each year, in particular those notified as septicaemia, rose significantly over the period (p < 0.0001) but there was no net change in the number of culture confirmed cases . Case fatality rates estimated from routine data fell, most markedly for cases notified as septicaemia, but the true case fatality rate of culture confirmed cases did not change between 1993 and 1995 . These data suggest that reporting practice changed between 1989 and 1995 and that the ascertainment of clinically diagnosed disease improved, particularly for meningococcal septicaemia . Late in 1995, reports from all data sources increased and the age distribution of both notified and laboratory confirmed cases changed . These changes were accompanied by an increase in the proportion of infections due to Neisseria meningitidis of serogroup C and a significant increase in serotype C2a infections (p < 0.0001) . Continuing efforts to reconcile data from several sources will be needed to ensure that routine data can be interpreted accurately to provide evidence for the development of future vaccination policy and to monitor vaccination programmes . In addition, the role of non-culture diagnosis will be crucial in enhancing surveillance based on clinical diagnoses. Nervenarzt, 1997 Apr, 68(4), 331 - 5 {Frequent problems with antibiotic chemotherapy of bacterial CNS diseases . Case reports and recommendations for initial treatment}; Bitsch A et al.; The initial antibiotic treatment of bacterial meningoencephalitis has major implications for the course of the disease . The current spectrum of infectious agents must be considered . Antibiotics have to reach sufficient concentrations in the blood and cerebrospinal fluid for a bactericidal action to occur at the site of infection . Frequent problems arising in this condition are: (1) the non-observation of listerial infections, (2) the use of antibiotics not sufficiently active against gram-positive bacteria in pneumococcal meningitis, (3) the development of meningitis following the use of ciprofloxacin in respiratory tract infections, (4) the hasty change in antibiotic regimens in focal parenchymal infections during delayed response to therapy, (5) the use of bacteriostatic antibiotics, and (6) the delay in administering sufficient antibiotic therapy during fulminate meningococcal meningitis . Problems arising from these conditions are illustrated by case reports. An Esp Pediatr, 1997 Apr, 46(4), 325 - 7 {Neisseria meningitidis strains with decreased susceptibility to penicillin and ampicillin}; Quiles Dura JL et al.; Thirty-eight patients (31 children and 7 adults) with meningococcal infection (sepsis and/or meningitis) were studied . The strain most frequently isolated was B (44.7%), followed by C (31.6%) . Of the strains isolated, 52.6% were moderately resistant to penicillin (91.6% if only strain C was considered) . No resistance to cephotaxime or chloramphenicol was found . Even though patients with moderately resistant strains treated with penicillin G evolved satisfactorily (minimum inhibitory concentrations 0.12-0.50 microgram/ml), the possible appearance of more resistant strains and/or of strains that produce beta-lactamase leads us to the conclusion that cephotaxime is the treatment of choice until an antibiogram is available. Nihon Kyobu Shikkan Gakkai Zasshi, 1997 Apr, 35(4), 461 - 5 {Bronchopneumonia caused by Neisseria meningitidis--probable transmission by a family member who had been in Hong Kong}; Ohtaki M et al.; A 22-year-old man came to our hospital complaining of bloody sputum . No abnormalities were seen on a chest X-ray film, but computed tomography of the chest showed infiltrates in the middle and lower lung fields . Neisseria meningitidis was isolated from cultured samples of naso pharyngeal secretions, from sputum, and from a sample obtained during bronchoscopy; bacterial bronchopneumonia was diagnosed . Family members were studied for meningococcal infection, and the bacterium was cultured from a nasopharyngeal smear from the patient's mother . The mother was asymptomatic . Both bacteria belonged to Group B serum group and their drug sensitivities were equal . The patient's family had been in Hong Kong, where this bacterium is endemic, for two years . They then returned to Japan and started to live together with the patient nine months before the onset of symptoms . The mother may have become infected in Hong Kong and may have passed the bacterium to her son after her return . Oral ampicillin was effective in both mother and son . Investigation of the patient's family was necessary to establish the probable route of infection and to decide on the treatment. Vaccine, 1997 Apr-May, 15(6-7), 751 - 8 Recombinant Opc meningococcal protein, folded in vitro, elicits bactericidal antibodies after immunization; Musacchio A et al.; The meningococcal Opc protein has been expressed as inclusion bodies in Escherichia coli . After cell disruption and successive washing of the insoluble fraction, insoluble proteins were solubilized in presence of the chaotropic agent guanidium hydrochloride . The extract was applied to a Reverse Phase High Performance Liquid Chromatography (RP-HPLC)-C4 column, for further purification . The obtained recombinant Opc protein was refolded in vitro, by the addition of several compounds to the resuspended solution . Over time, the progress of renaturation was tested by immunoblot with the human monoclonal antibody LuNm03 against the meningococcal Opc protein . LuNm03 recognizes a conformational epitope on the native meningococcal Opc protein . Having established the optimal conditions of renaturation . Balb/c mice were immunized to study the humoral immune response . The human at immune response elicited in mice was measured by ELISA and immunoblot, while the functional activity of these antibodies was assayed in a bactericidal test . According to our results, it was possible to obtain a recombinant Opc protein folded in vitro, with a conformation suitable enough to generate functional antibodies in mice, capable of killing meningococci in the presence of human complement. Epidemiol Infect, 1997 Apr, 118(2), 111 - 7 Non-culture diagnosis and serogroup determination of meningococcal B and C infection by a sialyltransferase (siaD) PCR ELISA; Borrow R et al.; Rapid, non-culture, serogroup determination of meningococcal infection is important in contact management where vaccination may be possible . The impending availability of polysaccharide-protein conjugate vaccines for serogroup C disease requires maximal case ascertainment, with serogroup determination, at a time when the number of culture confirmed meningococcal infections is decreasing . A polymerase chain reaction assay (PCR), based on a restriction fragment length polymorphism (RFLP) in the meningococcal serogroup B and C sialytransferase (siaD) gene, was developed to combine the non-culture diagnosis of meningococcal infection from CSF, whole blood and serum with serogroup (B and C) identification . The PCR assay was adapted to an ELISA format incorporating hybridization with serogroup-specific B and C oligonucleotide probes . Specificity for CSFs was 100% and sensitivities were respectively 81, 63 and 30% for CSFs, whole blood and sera . The serogroup-specific PCR ELISA is a significant addition to currently available tests for non-culture diagnosis of meningococcal infection and outbreak investigation. Arch Med Res, 1997 Spring, 28(1), 37 - 40 Biodistribution of the Cuban anti-meningococcal vaccine, VA-MENGOC-BC, in Balb/c mice; Perez-Martin O et al.; VA-MENGOC-BC is the Cuban vaccine against Neisseria meningitidis BC . Its iodination and biodistribution measurement in Balb/c mice were the main goals of this study . The Chloramine-T method was effective for radiolabelling the proteoliposome, the main vaccine structure . The biodistribution demonstrated that the thyroid (50.4%), muscle (21.5%) and regional lymph nodes (20.5%) were the most radioactive organs and the kinetic of radioactivity was correlated with the primary (muscle, highest values in the first 3 days and lymph nodes, in the first 7 days) and secondary (muscle and lymph nodes, highest values in the first day) response . Early occurrence of slight radioactivity in the spleen was also observed . This was the first time that the iodination and biodistribution of this vaccine was carried out . The present study corroborated that the time selected in previous trials to obtain the lymph nodes and spleen cell, after a first (7 days) and second (3 days) dose, was actually the optimal for in vitro studies. Carbohydr Res, 1997 Mar 5, 298(3), 191 - 9 Structural basis of the Neisseria meningitidis immunotypes including the L4 and L7 immunotypes; Kogan G et al.; The application of high-resolution 1H, 13C and 31P NMR and MS analyses to the oligosaccharide moieties of the L4 and L7 immunotypes of Neisseria meningitidis revealed that they had the following structures: {formula: see text} The fact that the L7 LPS is not sialylated at O-3 of its terminal beta-D-galactopyranosyl residue implies that it is a mutant strain unable to endogenously sialylate its lacto-N-neotetraose antenna . With the structural elucidation of the L4 and L7 LPS immunotypes, a more comprehensive structural profile of the LPS involved in disease isolates can now be assembled . This provides valuable insights into the structural basis of the N . meningitidis immunotyping system which could be of use in formulating an LPS-based vaccine against meningococcal meningitis. Zh Mikrobiol Epidemiol Immunobiol, 1997 Mar-Apr, (2), 24 - 9 {The isolation and immunochemical characteristics of the basic iron-regulated protein in meningococci}; Filatova TN et al.; A sufficiently simple and easy method for the isolation of one of the basic meningococcal iron-regulated proteins (IRP), protein with a mol . wt . of 37 kD (IRP 37), was developed . To carry out fine chromatographic purification of this protein . Russian-made cation-exchange sorbents, synthesized on the basis of silica gels with chemically bound functional groups, were used . The use of such sorbents made it possible to isolate IRP in water-saline solutions . The study of the immunological properties of IRP 37 revealed that antibodies to IRP 37 were specific only to mouse and rabbit meningococcal antisera and were not detected in animal antisera to a number of other pathogenic and opportunistic bacteria . The study also revealed that antibodies to this protein were present in all examined sera of patients with meningococcal meningitis . The conclusion was made that IRP 37 presented considerable interest for the immunodiagnostics and immunoprophylaxis of meningococcal and, probably, gonococcal infections. An Esp Pediatr, 1997 Mar, 46(3), 233 - 6 {Meningococcal infection: changes in serogroups and penicillin resistance}; Osona Rodriguez B et al.; OBJECTIVE: There has been an increasing number of strains of meningococcus with reduced susceptibility to penicillin in Spain during the past few years . The serogroup distribution has also changed during this period . The objective of this study was to estimate the incidence of different N . meningitidis serogroups, the penicillin susceptibility and the clinical and laboratory data from the patients with meningococcal disease in our hospital . PATIENTS AND METHODS: A retrospective study of the patients admitted to the hospital during a 4 year period (1993-1996) with bacteriological data of meningococcal sepsis/meningitis was performed . Serogroup and penicillin minimum inhibitory concentration (MIC) were determined . Analysis of the clinical data from the patients with disease due to serogroups B or C was also performed . RESULTS: The incidence of serogroups C and B was 47% and 51.6%, respectively . There were 5 cases of decreased susceptivility to penicillin (MIC 0 0.25 microgram/ml) . There were no clinical differences between the two groups of patients . CONCLUSIONS: There was a progressive increase in the incidence of serogroup C, while the incidence of serogroup B remained stable, as did the cases of meningococci with reduced susceptibility to penicillin . Although this study did not suggest a modification in the initial treatment, every strain of meningococci must be studied to show penicillin MIC to avoid treatment failure. Diagn Microbiol Infect Dis, 1997 Mar, 27(3), 93 - 7 Comparative evaluation of etest for susceptibility testing Neisseria meningitidis with eight antimicrobial agents . An investigation using U.S . Food and Drug Administration regulatory criteria; Marshall SA et al.; Invasive infections caused by Neisseria meningitidis continue to be a serious clinical problem for therapy, epidemiology, and potential prophylaxis . Multiple antimicrobial resistances have emerged among meningococcal strains including elevated MICs to penicillin, sulfonamides, tetracyclines, and rifampin . Thus, the need to perform accurate susceptibility testing of meningococci in clinical practice and for surveillance programs has renewed priority . In this study, for the first time Etest (AB Biodisk, Solna, Sweden) was compared to a reference agar dilution method using a large number (100) of clinical strains selected for a range of drug resistances . Etest quantitative accuracy (+/-one log2 dilution agreement) ranged from 94% (penicillin) to 100% (three drugs) for the eight clinically useful antimicrobial agents tested . Intermethod categorical accuracy for all drug ranged from 92% (penicillin, erythromycin) to 100% (five drugs), without false-susceptible or -resistant errors using Etest . Etest and reference methods were highly reproducible (99.6 to 100.0%, respectively) . Quantitative discords between methods (> or = two log2 dilutions) were not reproducible and resolved following repeated testing . Etest method proved to be an accurate and reproducible quantitative method for testing N . meningitidis strains for the compared antimicrobial agents (eight) often utilized for therapy and prophylaxis of serious meningococcal disease. J Infect, 1997 Mar, 34(2), 101 - 5 Meningococcal carriage: prevalence and sex-related risk factors; Tayal SC et al.; A retrospective analysis was done to examine whether sexual behaviour was associated with meningococcal carriage . Over the 4 month period from January to April 1994, 136 (27.4%) of the 496 consecutive new/re-registered genito-urinary medicine clinic attenders showed meningococcal carriage . Two (15.4%) of 13 homosexual men compared with 134 (27.7%) of 484 heterosexual men and women had evidence of meningococcal carriage . Relative risk (RR) of meningococcal carriage was 1.8 with > 10 lifetime partners and 1.2 with 3-10 partners (P < 0.007) . RR with age group of 16-25 was 4.2 and for 26-35 it was 3.5 . There was no relationship with meningococcal carriage and pharyngeal symptoms, sexual orientation, intravenous drug use, number of partners per month and orogenital sex . Further longitudinal studies may be of value in order to determine whether a high number of sexual partners is a marker for meningococcal carriage . In addition, further study may show whether there is an increased risk of meningococcal carriage and disease in those who live with meningococcal carriers. Neth J Med, 1997 Mar, 50(3), 102 - 4 Chronic meningococcaemia: a case report; Kruijtzer CM et al.; Chronic meningococcaemia (CM), caused by the bacterium Neisseria meningitidis is reported in a 27-year-old Indonesian man . The main symptoms were intermittent fever, skin rash and arthralgia . The pathogenesis, symptoms, differential diagnoses and treatment of CM are discussed. Clin Infect Dis, 1997 Mar, 24(3), 452 - 5 Osteonecrosis following meningococcemia and disseminated intravascular coagulation in an adult: case report and review; Campbell WN et al.; Meningococcemia and disseminated intravascular coagulation (DIC) have a known association, and they have been identified as a rare cause of osteonecrosis in children . To our knowledge, we report only the second case of an adult with DIC and Neisseria meningitidis infection whose condition was subsequently diagnosed as osteonecrosis . We also review the world medical literature that pertains to osteonecrosis as a sequelae of meningococcal infection associated with DIC. FEMS Immunol Med Microbiol, 1997 Mar, 17(3), 139 - 48 Epitope specificity of murine and human bactericidal antibodies against PorA P1.7,16 induced with experimental meningococcal group B vaccines; Rouppe van der Voort EM et al.; Synthetic peptides derived from the predicted loops 1 and 4 of meningococcal PorA, sero-subtype P1.7,16, were used to study the epitope specificity of murine and human PorA P1.7,16 bactericidal antibodies . The predicted loops 1 and 4 are surface exposed and carry in their apices the sero-subtype epitopes P1.7 (loop 1) or P1.16 (loop 4), respectively . Peptides were synthesized as mono- and multimeric peptides . Murine monoclonal and polyclonal antibodies were induced with meningococcal whole cell preparations . Polyclonal antibodies were evoked in volunteers after one immunization with 50 micrograms or 100 micrograms protein of a hexavalent meningococcal PorA vesicle vaccine . The induction of PorA antibodies was determined in ELISA using purified PorA P1.7,16 . The epitope specificity of anti-PorA antibodies for both murine and human antibodies could be demonstrated by direct peptide ELISA using overlapping multimeric peptides almost spanning the entire loops 1 or 4 of the protein . The capacity of peptides to inhibit the bactericidal activity of murine and human antibodies was investigated using meningococcal strain H44/76 (B:15:P1.7,16) as a target strain . Bactericidal activities could be inhibited with both monomeric and multimeric peptides derived from epitopes P1.7 and P1.16. Infect Control Hosp Epidemiol, 1997 Mar, 18(3), 203 - 4 Nosocomial Neisseria meningitidis: molecular analysis of a clinical problem; Louie M et al.; Over a 1-week period, Neisseria meningitidis serogroup B was recovered from two patients in the intensive-care unit (ICU) . A cross-infection was presumed when one patient developed invasive meningococcal disease and another patient was found to be colonized . Investigation by molecular typing showed that these cases were not related, demonstrating the value of molecular typing when investigating potential cross-infections in a closed environment such as the ICU. Can J Microbiol, 1997 Mar, 43(3), 234 - 8 Subtyping of Neisseria meningitidis strains isolated in Quebec, Canada: correlation between deduced amino acid sequences and serosubtyping techniques; Arhin FF et al.; Routine serosubtyping of Neisseria meningitidis relies upon reactivity of whole cells to monoclonal antibodies (mAbs) . This procedure is limited in providing maximum serosubtype information because some epitopes in whole cells are masked and because mAbs are currently unavailable for some epitopes . To address masking of epitopes in whole cells, we isolated outer membrane vesicles (OMVs) from nine representative meningococcal strains that were isolated (1991-1993) in the province of Quebec, Canada; the OMVs were used in enzyme-linked immunosorbent assay for reactivity to mAbs, and improved serosubtyping information was obtained . A recent proposal assigns subtypes based on deduced amino acid sequences in the variable regions of the class 1 outer membrane protein . This scheme maintains the subtyping nomenclature that is based on reactivity to mAbs by defining the sequences in the epitopes recognized by the mAbs . We used this technique to assign subtypes to the meningococcal strains isolated in Quebec . For the strains tested, serosubtyping using mAbs and subtyping based on deduced amino acid sequences were in complete agreement . Subtyping using deduced amino acid sequences is superior because it does not depend on the availability of mAbs. Ann Plast Surg, 1997 Mar, 38(3), 283 - 90 Treatment of thromboembolic complications of fulminant meningococcal septic shock; Mele JA 3rd et al.; A patient report of fulminant meningococcal septic shock is described . The presentation, hospital course, and reconstructive efforts are outlined, and a brief review of meningococcal infection is included . Emphasis is placed on the algorithm used to determine treatment . A 19-year-old Hispanic male presented with all the hallmarks of Waterhouse-Friderichsen syndrome (WFS)-sudden onset, high fever, dyspnea with intermittent cyanosis, shock, disseminated intravascular coagulopathy, and the development of purpura . The pathognomonic feature of WFS-hemorrhage into the adrenal glands-if present, was not extensive, as he did not require steroid supplementation . Though cerebrospinal fluid latex agglutination was negative, his serum was positive for group C Neisseria and admission blood cultures grew Neisseria meningitidis . Thromboembolic complications were systemic with the highest morbidity peripherally in the lower extremities . Care for these injuries involved every rung of the reconstructive ladder-from local wound care and skin grafts to local flaps and microvascular transplantation. Mol Microbiol, 1997 Mar, 23(5), 879 - 92 PilC of Neisseria meningitidis is involved in class II pilus formation and restores pilus assembly, natural transformation competence and adherence to epithelial cells in PilC-deficient gonococci; Ryll RR et al.; Type 4 pili produced by the pathogenic Neisseria species constitute primary determinants for the adherence to host tissues . In addition to the major pilin subunit (PilE), neisserial pili contain the variable PilC proteins represented by two variant gene copies in most pathogenic Neisseria isolates . Based upon structural differences in the conserved regions of PilE, two pilus classes can be distinguished in Neisseria meningitidis . For class I pili found in both Neisseria gonorrhoeae and N . meningitidis, PilC proteins have been implicated in pilus assembly, natural transformation competence and adherence to epithelial cells . In this study, we used primers specific for the pilC2 gene of N.gonorrhoeae strain MS11 to amplify, by the polymerase chain reaction, and clone a homologous pilC gene from N . meningitidis strain A1493 which produces class II pili . This gene was sequenced and the deduced amino acid sequence showed 75.4% and 73.8% identity with the gonococcal PilC1 and PilC2, respectively . These values match the identity value of 74.1% calculated for the two N . gonorrhoeae MS11 PilC proteins, indicating a horizontal relationship between the N . gonorrhoeae and N . meningitidis pilC genes . We provide evidence that PilC functions in meningococcal class II pilus assembly and adherence . Furthermore, expression of the cloned N . meningitidis pilC gene in a gonococcal pilC1,2 mutant restores pilus assembly, adherence to ME-180 epithelial cells, and transformation competence to the wild-type level . Thus, PilC proteins exhibit indistinguishable functions in the context of class I and class II pili. Clin Diagn Lab Immunol, 1997 Mar, 4(2), 156 - 67 Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays . The Multilaboratory Study Group; Maslanka SE et al.; A standardized serum bactericidal assay (SBA) is required to evaluate the functional activity of antibody produced in response to Neisseria meningitidis serogroup A and C vaccines . We evaluated assay parameters (assay buffer, target strains, growth of target cells, target cell number, complement source and concentration, and methods for growth of surviving bacteria) which may affect the reproducibility of SBA titers . The various assay parameters and specificity of anticapsular antibody to five serogroup A strains (A1, ATCC 13077, F8238, F9205, and F7485) and four serogroup C strains (C11, G7880, G8050, and 1002-90) were evaluated with Centers for Disease Control and Prevention meningococcal quality control sera . The critical assay parameters for the reproducible measurement of SBA titers were found to include the target strain, assay incubation time, and complement . The resulting standardized SBA was used by 10 laboratories to measure functional anticapsular antibody against serogroup A strains F8238 and serogroup C strain C11 . In the multilaboratory study, SBA titers were measured in duplicate for 14 pairs of sera (seven adults and seven children) before and after immunization with a quadrivalent polysaccharide (A, C, Y, and W-135) vaccine . The standardized SBA was reliable in all laboratories regardless of experience in performing SBAs . For most sera, intralaboratory reproducibility was +/- 1 dilution; interlaboratory reproducibility was +/- 2 dilutions . The correlation between median titers (interlaboratory) and enzyme-linked immunosorbent assay total antibody concentrations was high for both serogroup A (r = 0.86; P < 0.001; slope = 0.5) and serogroup C (n = 0.86; P < 0.001; slope = 0.7) . The specified assay, which includes the critical parameters of target strain, incubation time, and complement source, will facilitate interlaboratory comparisons of the functional antibody produced in response to current or developing serogroup A and C meningococcal vaccines. J Clin Microbiol, 1997 Mar, 35(3), 745 - 50 Genetic analysis of a meningococcal population based on polymorphism of the pilA-pilB locus: a molecular approach for meningococcal epidemiology; Guibourdenche M et al.; The genetic relationships between 88 meningococcal strains were analyzed by using the polymorphism of the pilA gene and the multilocus enzyme electrophoresis . While a good agreement was observed, correlation with antigenic formula (serogroup, serotype, and serosubtype) was incomplete . The inadequacy of serological classification alone in outbreak surveillance may be overcome by DNA-based approaches. Infect Immun, 1997 Mar, 65(3), 1053 - 60 Bactericidal antibody responses of juvenile rhesus monkeys immunized with group B Neisseria meningitidis capsular polysaccharide-protein conjugate vaccines; Zollinger WD et al.; Reports on the bactericidal activities of antibodies to group B Neisseria meningitidis capsular polysaccharide (B PS) are conflicting . Using three different complement sources, we analyzed the bactericidal activities of sera of juvenile rhesus monkeys immunized with five conjugate vaccines of B PS synthesized by different schemes, an Escherichia coli K92 conjugate, and a noncovalent complex of B PS with group B meningococcal outer membrane vesicles (B+OMV) (S . J . N . Devi, W . D . Zollinger, P . J . Snoy, J . Y . Tai, P . Costantini, F . Norelli, R . Rappuoli, and C . E . Frasch, Infect . Immun . 65:1045-1052, 1997) . With rabbit complement, nearly all preimmune sera showed relatively high bactericidal titers, and all vaccines, except the K92 conjugate, induced a fourfold or greater increase in bactericidal titers in most of the monkeys vaccinated . In contrast, with human complement, most prevaccination sera showed no bactericidal activity and in most of the vaccine groups, little or no increase in bactericidal titer was observed . However, the covalent conjugation of P BS and OMV (B-OMV) administered with and without the Ribi adjuvant induced relatively high bactericidal titers which persisted up to 30 weeks . An analysis of the specificities of bactericidal antibodies revealed that absorption with E . coli K1 cells did not change the bactericidal titer with human complement but reduced the titers observed with the rabbit and monkey complements . A significant increase in anti-lipopolysaccharide (LPS) antibodies was elicited by the B-OMV conjugates, and nearly all of the bactericidal activity with human complement could be inhibited with the purified group B meningococcal L3,7,8 LPS . B-OMV covalently coupled via adipic acid dihydrazide elicited significantly elevated levels (P < or = 0.02) of anti-OMV antibodies compared to those of the noncovalently complexed B+OMV . An initial small-scale evaluation of B PS conjugates in adult human males appears feasible, with careful monitoring, to settle the inconsistent reports of the importance of source of complement in eliciting bacteriolysis . Subsequent analysis of resultant human antibodies for bacteriolysis, opsonophagocytosis, and protective efficacy in animal models may be the first step toward answering safety- and efficacy-related concerns about B PS conjugate vaccines. Infect Immun, 1997 Mar, 65(3), 1045 - 52 Preclinical evaluation of group B Neisseria meningitidis and Escherichia coli K92 capsular polysaccharide-protein conjugate vaccines in juvenile rhesus monkeys; Devi SJ et al.; We reported the first use of group B meningococcal conjugate vaccines in a nonhuman primate model (S . J . N . Devi, C . E . Frasch, W . Zollinger, and P . J . Snoy, p . 427-429, in J . S . Evans, S . E . Yost, M . C . J . Maiden, and I . M . Feavers, ed., Proceedings of the Ninth International Pathogenic Neisseria Conference, 1994) . Three different group B Neisseria meningitidis capsular polysaccharide (B PS)-protein conjugate vaccines and an Escherichia coli K92 capsular polysaccharide-tetanus toxoid (K92-TT) conjugate vaccine are here evaluated for safety and relative immunogenicities in juvenile rhesus monkeys with or without adjuvants . Monkeys were immunized intramuscularly with either B PS-cross-reactive material 197 conjugate, B PS-outer membrane vesicle (B-OMV) conjugate, or N-propionylated B PS-outer membrane protein 3 (N-pr . B-OMP3) conjugate vaccine with or without adjuvants at weeks 0, 6, and 14 . A control group of monkeys received one injection of the purified B PS alone, and another group received three injections of B PS noncovalently complexed with OMV . Antibody responses as measured by enzyme-linked immunosorbent assay varied among individual monkeys . All vaccines except B PS and the K92-TT conjugate elicited a twofold or greater increase in total B PS antibodies after one immunization . All vaccines, including the K92-TT conjugate, elicited a rise in geometric mean B PS antibody levels of ninefold or more over the preimmune levels following the third immunization . Antibodies elicited by N-pr . B-OMP3 and B-OMV conjugates were directed to the N-propionylated or to the spacer-containing B PS antigens as well as to the native B PS complexed with methylated human serum albumin . None of the vaccines caused discernible safety-related symptoms. Lancet, 1997 Feb 15, 349(9050), 466 - 9 Extracorporeal support for intractable cardiorespiratory failure due to meningococcal disease; Goldman AP et al.; BACKGROUND: Meningococcal disease is still associated with considerable mortality, despite the use of early antibiotics and management in specialised intensive care units, due principally to early refractory myocardial depression and hypotension as well as severe acute respiratory distress syndrome . Extracorporeal membrane oxygenation (ECMO) is a complex technology that uses a modified "heart-lung" machine to provide temporary cardiac and respiratory support . We reviewed the UK and Australian experience of the use of ECMO in patients with refractory cardiorespiratory failure due to meningococcal disease . METHODS: The records from all 12 known patients supported with ECMO for meningococcal disease in the UK and Australia since 1989 were reviewed . FINDINGS: 12 patients (aged 4 months to 18 years, median 26 months) with meningococcal disease received ECMO over 8 years . In seven patients, ECMO was required early for cardiac support for intractable shock within 36 h of admission to intensive care . In the other five patients, ECMO was indicated for respiratory failure due to severe adult respiratory distress syndrome, which tended to occur later in the disease . The paediatric risk of mortality score ranged from 13 to 40 (median 29, median predicted risk of mortality 72%) . Six of the 12 patients required cardiopulmonary resuscitation before ECMO and the other six were deteriorating despite maximal conventional therapy . Overall, eight of the 12 patients survived, with six leading functionally normal lives at a median of 1 year (range 4 months to 4 years) of follow-up . INTERPRETATION: ECMO might be considered to support patients with intractable cardiorespiratory failure due to meningococcal disease who are not responding to conventional treatment. MMWR Recomm Rep, 1997 Feb 14, 46(RR-5), 13 - 21 Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks: recommendations of the Advisory Committee on Immunization Practices (ACIP); Control and prevention of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP); These recommendations update information regarding the polysaccharide vaccine licensed in the United States for use against disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135, as well as antimicrobial agents for chemoprophylaxis against meningococcal disease (superseding MMWR 1985;34:255-9) . This report provides additional information regarding meningococcal vaccines and the addition of ciprofloxacin and ceftriaxone as acceptable alternatives to rifampin for chemoprophylaxis in selected populations. JAMA, 1997 Feb 5, 277(5), 389 - 95 School-based clusters of meningococcal disease in the United States . Descriptive epidemiology and a case-control analysis; Zangwill KM et al.; OBJECTIVE: To evaluate the epidemiologic features and risk factors for multiple cases of meningococcal disease in schools . DESIGN: Population-based prospective evaluation and case-control study of clusters of meningococcal disease that occurred in schools from January 1989 to June 1994 . SETTING: Surveillance conducted through state health departments in the United States . MAIN OUTCOME MEASURES: Descriptive epidemiology of school-based clusters of meningococcal disease and determinants of their occurrence . RESULTS: We identified 22 clusters of meningococcal disease in 15 states . The estimated incidence of secondary meningococcal disease among schoolchildren aged 5 to 18 years was 2.5 per 100000 population, a relative risk of 2.3 (95% confidence interval {CI}, 1.6-3.3) . The median number of students per cluster was 2 (range, 2-4) . Of 30 subsequent cases, 10 (33%) occurred 2 or fewer days after the index case, and 22 (73%) occurred 14 or fewer days after the index case . Among the 8 schools with 2 or more cases, 50% of the additional cases occurred 2 or more days after the second case . Secondary schools (grades 7 through 12) accounted for 15 (75%) of 20 cluster schools compared with 9 (45%) of 20 matched control schools (P<.05) . In 16 (73%) of 22 clusters, interaction between case patients was noted . The index patient in cluster schools was more likely than the controls to have participated in a school-based group activity 14 or fewer days before illness (matched odds ratio, 7.0; 95% CI, 0.9-57) . CONCLUSIONS: Three quarters of the school clusters occurred in secondary schools, with over 70% of subsequent cases occurring within 2 weeks of the index case . Rapid initiation of a chemoprophylaxis program after 2 cases of meningococcal disease in a school would have potentially prevented 50% of subsequent cases in the clusters described. J Infect Dis, 1997 Feb, 175(2), 364 - 72 Preclinical evaluation of a novel group B meningococcal conjugate vaccine that elicits bactericidal activity in both mice and nonhuman primates; Fusco PC et al.; Group B meningococcal (GBM) conjugate vaccines were prepared using chemically modified N-propionylated polysialic acid, from Escherichia coli K1 polysaccharide capsule, coupled by reductive amination to tetanus toxoid and purified recombinant GBM porin (rPorB) . All conjugates elicited high antibody levels in mice with good booster responses . However, only rPorB conjugates elicited bactericidal activity specific against a broad spectrum of five different GBM serotypes . Bactericial activity was completely inhibited by free N-propionylated polysaccharide . In baboons and rhesus monkeys, rPorB conjugates elicited high antibody titers, with IgG booster responses 9- to 15-fold higher than primary responses . Bactericial activity increased 19- to 39-fold over preimmune values, using rabbit complement; increased bactericial activity was also confirmed with human and monkey complement . IgG cross-reactivity for unmodified N-acetyl polysaccharide was <5% for 79% of mice and <10% for 80% of primates . These studies strongly suggest that the N-propionylated polysialic acid-rPorB conjugate is an excellent vaccine candidate for human use. Inflammation, 1997 Feb, 21(1), 69 - 82 Alpha-1-acid (AAG, orosomucoid) glycoprotein: interaction with bacterial lipopolysaccharide and protection from sepsis; Moore DF et al.; In the acute phase response to a variety of insults a rise in the levels of the acute phase proteins, including elevations of serum alpha 1 acid glycoprotein (AAG) occurs . The physiological role of AAG is unknown, however, the time course of AAG production in the acute phase response together with its strong affinity for basic compounds suggests that AAG may function as an immune modulator to bind both exogenous and endogenous inflammatory mediators . Using E . coli lipopolysaccharide (LPS), an initiator of the acute inflammatory response associated with septic shock, we demonstrate that AAG-LPS complexes can activate mouse macrophages in vitro . In a mouse animal model of sepsis, AAG was shown to protect against meningococcal endotoxin . To pursue the mechanism of AAG action we demonstrated that AAG interacts directly with LPS using dynamic light scattering particle sizing and particle mobility . We also determined the enthalpy of interaction of AAG and LPS and showed that AAG leads to agglutination of LPS impregnated rabbit red blood cells . These studies suggest that AAG may function as an immune-modulator in the acute phase response, possibly by counter-regulating the activity of macrophage pro-inflammatory cytokines. Mol Microbiol, 1997 Feb, 23(4), 799 - 812 Interspecies recombination, and phylogenetic distortions, within the glutamine synthetase and shikimate dehydrogenase genes of Neisseria meningitidis and commensal Neisseria species; Zhou J et al.; Visual inspection showed clear evidence of a history of intraspecies recombinational exchanges within the neighbouring meningococcal shikimate dehydrogenase (aroE) and glutamine synthetase (glnA) genes, which was supported by the non-congruence of the trees constructed from the sequences of these genes from different meningococcal strains, and by statistical tests for mosaic structure . Many examples were also found of highly localized interspecies recombinational exchanges between the meningococcal aroE and glnA genes and those of commensal Neisseria species . These exchanges appear to have inflated the sequence variation at these loci, and have resulted in major distortions of the phylogenetic trees constructed from the sequences of the aroE and glnA genes of human pathogenic and commensal Neisseria species . Statistical tests for sequence mosaicism, and for anomalies within the Neisseria species trees, strongly supported the view that frequent interspecies recombination has occurred within aroE and glnA . The high levels of sequence variation, and intra- and interspecies recombination, within aroE and glnA did not appear to be due to a 'hitch-hiking' effect caused by positive selection for variation at a neighbouring gene . Our results suggest that interspecies recombinational exchanges with commensal Neisseria occur frequently in some meningococcal 'housekeeping' genes as they can be observed readily even when there appears to be no obvious selection for the recombinant phenotypes. Mol Microbiol, 1997 Feb, 23(4), 737 - 49 Molecular characterization of hpuAB, the haemoglobin-haptoglobin-utilization operon of Neisseria meningitidis; Lewis LA et al.; We previously identified HpuB, an 85 kDa Fe-repressible protein required for utilization of Fe from, and binding to, haemoglobin and the haemoglobin-haptoglobin complex . The gene for hpuB was cloned from Neisseria meningitidis strain DNM2 and the predicted amino acid sequence indicates that HpuB is an outer membrane receptor belonging to the TonB family of high-affinity transport proteins . A second open reading frame, predicted to encode a 34.8 kDa lipoprotein, was discovered 5' to hpuB, and was designated hpuA . HpuA was identified in a total-membrane-protein preparation by construction of a mutant lacking HpuA . Acylation of HpuA was confirmed by {3H}-palmitic acid labelling of meningococci . Consensus promoter sequences were not apparent 5' to hpuB . The hpuA insertion mutation exerted a polar effect, abolishing expression of hpuB, suggesting that hpuA and hpuB are co-transcribed . The 3.5 kb polycistronic hpuAB mRNA was identified and shown to be transcriptionally repressed by iron . The transcriptional start site was identified 33 nucleotides 5' to the hpuA translational start site, appropriately positioned around consensus promoter and ferric uptake regulator (Fur)-box sequences . The structure of this operon suggests that HpuA-HpuB is a two-component receptor analogous to the bipartite transferrin receptor TbpB-TbpA. APMIS, 1997 Feb, 105(2), 150 - 6 Decreased plasma levels of factor II + VII + X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections; Bygbjerg IC et al.; The levels of coagulation factors II + VII + X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in the patients with malaria or meningococcal infections . The coagulation factors were decreased particularly in the meningococcal patients, while thrombocytes were lowest in the Plasmodium falciparum malaria patients . There was no correlation between factors II + VII + X and thrombocytes, but plasma levels of coagulation factors II + VII + X were found to correlate inversely with levels of soluble interleukin-2 receptor (sIL-2R) and soluble tumour necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections . Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P . falciparum patients followed consecutively . Estimation of coagulation factors may be used to monitor the course of these common and potentially life-threatening infections. Arch Dis Child, 1997 Feb, 76(2), 134 - 8 Hearing loss during bacterial meningitis; Richardson MP et al.; OBJECTIVE: To determine the natural history and pathogenesis of hearing loss in children with acute bacterial meningitis . DESIGN: Multicentre prospective study . SETTING: 21 hospitals in the south and west of England and South Wales . SUBJECTS: 124 children between the ages of 4 weeks and 16 years with newly diagnosed bacterial meningitis . METHODS: Children underwent repeated audiological assessment with the first tests being performed within six hours of diagnosis . By using a combination of otoacoustic emissions, auditory brainstem responses, and tympanometry the differences between cochlear, neural, and conductive defects were distinguished . RESULTS: Ninety two children (74%) had meningococcal and 18 (15%) had pneumococcal meningitis . All cases of hearing loss were apparent at the time of the first assessment . Three children (2.4%, 95% confidence interval (CI) 0.5 to 6.9%) had permanent sensorineural hearing loss . Thirteen children (10.5%) had reversible hearing loss of whom nine had an impairment that resolved within 48 hours of diagnosis . It is believed that this "fleeting' hearing loss has not been reported previously . The cochlea was identified as the site of the lesion in both the permanent sensorineural and reversible impairments . Hearing loss was more common in children who had been ill for more than 24 hours (relative risk 2.72; 95% CI 0.93 to 7.98) . CONCLUSIONS: Sensorineural hearing loss developed during the earliest stages of meningitis . Permanent deafness was rare but 10% of the patients had a rapidly reversible cochlear dysfunction . This may have progressed to permanent deafness if the patients had not been treated promptly. J Bacteriol, 1997 Feb, 179(3), 831 - 7 Adaptation to sulfonamide resistance in Neisseria meningitidis may have required compensatory changes to retain enzyme function: kinetic analysis of dihydropteroate synthases from N . meningitidis expressed in a knockout mutant of Escherichia coli; Fermer C et al.; Previously, the effects of three point mutations (at amino acid positions 31, 84, and 194) in the gene coding for a sulfonamide-resistant dihydropteroate synthase of Neisseria meningitidis were analyzed by site-directed mutagenesis . Changes at positions 31 and 194 abolished the phenotypic expression of sulfonamide resistance, while a change at position 84 appeared to be neutral . These studies are here extended to correlate the alterations in phenotype with effects on enzyme kinetics by expressing the cloned meningococcal genes in an Escherichia coli strain that had its dhps gene partially deleted and replaced by a resistance determinant . The most dramatic effects were produced by mutations at position 31 . A change from the Leu found in the resistant isolate to a Phe (the residue found in sensitive isolates) led to a 10-fold decrease in the Km and a concomitant drop in the Ki . Changes at position 194 also affected both the Km and Ki but not to the same extent as mutations at position 31 . Changing position 84 altered the Km only slightly but significantly . This latter change was interpreted as a compensatory change modulating the function of the enzyme . In another type of resistance gene, 2 amino acid residues, proposed to be an insertion, were deleted, resulting in a sensitive enzyme . However, the resulting Km was raised 10-fold, suggesting that compensatory changes have accumulated in this type of resistance determinant as well . This resistance gene differs by as much as 10% from the sensitive isolates, which makes identification of important mutations difficult. Lancet, 1997 Jan 18, 349(9046), 170 - 3 Genetic influence on cytokine production and fatal meningococcal disease; Westendorp RG et al.; BACKGROUND: To assess the genetic influence on cytokine production and its contribution to fatal outcome, we determined the capacity to produce tumour necrosis factor-alpha (TNF alpha) and interleukin-10 (IL-10) in families of patients who had had meningococcal disease . METHODS: We studied 190 first-degree relatives of 61 patients with meningococcal disease; we also studied 26 monozygotic twins . Production of cytokines was determined during endotoxin stimulation of whole-blood samples ex-vivo . Heritability was estimated in a pedigree-based maximum-likelihood model . DNA was typed for the G to A transition polymorphisms at position -308 and -238 in the TNF gene promoter . FINDINGS: Heritability in monozygotic twins was 0.60 for the production of TNF and 0.75 for the production of IL-10 . Families with low TNF production had a tenfold increased risk for fatal outcome (OR 8.9, 95% CI 1.8-45), whereas high IL-10 production increased the risk 20-fold (19.5, 2.3-165) . Families with both characteristics had the greatest risk . The transition polymorphisms in the TNF gene promoter were not associated with outcome . INTERPRETATION: Genetic factors substantially influence production of cytokines . An innate anti-inflammatory cytokine profile may contribute to fatal meningococcal disease. J Immunol Methods, 1997 Jan 15, 200(1-2), 55 - 68 Functional assays for evaluation of serogroup B meningococcal structures as mediators of human opsonophagocytosis; Lehmann AK et al.; Functional flow cytometry and chemiluminescence (CL) assays have been modified to identify serogroup B meningococcal structures that mediate anti-meningococcal opsonophagocytosis . Serogroup B meningococcal outer membrane vesicles (OMV) were adsorbed to fluorescent latex beads (OMV-beads) and opsonized with acute phase and convalescence sera from patients with serogroup B meningococcal disease . Phagocytosis of these beads by human monocytes and polymorphonuclear leukocytes (non-lymphocytes) was dependent on both antigen exposure on the bead surface and on serum opsonization . OMV-beads opsonized with serum from a patient recovering from meningococcal disease, caused 97% of the non-lymphocytes to phagocytose an average of 15.8 beads per cell with a CL response of 46,550 mVs, whereas opsonized control beads were phagocytosed by 19% of the non-lymphocytes with 1.1 beads per cell and a CL response of 53 mVs . Increased amounts of functional, anti-OMV opsonins were detected during infection, and opsonized OMV-beads elicited phagocyte responses of similar magnitude to those of opsonized whole meningococci . Phagocyte internalization of OMV-beads was confirmed by confocal laser scanning microscopy . We conclude that epitopes on the meningococcal outer membrane are recognized by anti-meningococcal opsonins in these functional phagocytosis assays, which provide a basis for subsequent evaluation of various purified bacterial components as mediators of human opsonophagocytic responses and hence future vaccine constituents. Commun Dis Rep CDR Rev, 1997 Jan 10, 7(1), R9 - 13 Meningococcal disease in the Republic of Ireland: 1995; Fogarty I et al.; Two hundred and nine culture confirmed cases of meningococcal disease were reported in the Republic of Ireland in 1995, using a new laboratory based surveillance system . The reported rate of 5.9/100000 population is one of the highest in western Europe, but the rate differed widely between regions . Fifty-three per cent of cases were female . Half of the cases occurred in four months (January, February, March, and December) . Nineteen cases (9%) died . The highest age specific incidence was in infancy (under 1 year) . Infections with serogroup B accounted for 105 cases (54%) and serogroup C 87 cases (45%) . We estimate that up to 30% of cases of meningococcal disease may be preventable when conjugate meningococcal group C vaccines become available, but cost benefit analyses will be required to determine how they should be employed. Commun Dis Rep CDR Rev, 1997 Jan 10, 7(1), R5 - 9 A college outbreak of group C meningococcal infection: how widely should investigation and prophylaxis extend? Riordan T. Neisseria meningitidis group C type 2b, P1.2, P1.5 caused an outbreak of four cases, two of whom were members of an agricultural college in Devon, and two outside contacts of students who were documented carriers of the outbreak strain . The identification of the outbreak was made more difficult by the fact that none of the three cases first linked with the college was culture positive and indeed only one of these was actually a member of the college . Carriage of the outbreak strain was significantly associated with residence in college and enrollment on one particular course . The question was raised of whether in outbreaks of this type control measures should be extended beyond the confines of the affected institution. Commun Dis Rep CDR Rev, 1997 Jan 10, 7(1), R3 - 5 Management of clusters of meningococcal disease . PHIS Meningococcus Working Group and Public Health Medicine Environmental Group; Stuart JM et al.; Guidance on the management of clustered cases of meningococcal disease has been revised following a review of the clusters that occurred in England and Wales between 1 April 1995 and 31 March 1996 . Public health action is indicated for confirmed and probable cases but not in response to possible cases . The importance of microbiological confirmation is re-emphasised . Intervention is recommended for defined target groups when two or more confirmed or probable cases occur in a preschool group or school within a four week period . We present a framework to assist in the management of clusters of invasive serogroup C infections in larger and less defined communities. Proc Natl Acad Sci U S A, 1997 Jan 7, 94(1), 271 - 6 Capsule switching of Neisseria meningitidis; Swartley JS et al.; The different sialic acid (serogroups B, C, Y, and W-135) and nonsialic acid (serogroup A) capsular polysaccharides expressed by Neisseria meningitidis are major virulence factors and are used as epidemiologic markers and vaccine targets . However, the identification of meningococcal isolates with similar genetic markers but expressing different capsular polysaccharides suggests that meningococcal clones can switch the type of capsule they express . We identified, except for capsule, isogenic serogroups B {(alpha2-->8)-linked polysialic acid} and C {(alpha2-->9)-linked polysialic acid} meningococcal isolates from an outbreak of meningococcal disease in the U . S . Pacific Northwest . We used these isolates and prototype serogroup A, B, C, Y, and W-135 strains to define the capsular biosynthetic and transport operons of the major meningococcal serogroups and to show that switching from the B to C capsule in the outbreak strain was the result of allelic exchange of the polysialyltransferase . Capsule switching was probably the result of transformation and horizontal DNA exchange in vivo of a serogroup C capsule biosynthetic operon . These findings indicate that closely related virulent meningococcal clones may not be recognized by traditional serogroup-based surveillance and can escape vaccine-induced or natural protective immunity by capsule switching . Capsule switching may be an important virulence mechanism of meningococci and other encapsulated bacterial pathogens . As vaccine development progresses and broader immunization with capsular polysaccharide conjugate vaccines becomes a reality, the ability to switch capsular types may have important implications for the impact of these vaccines. Pathobiology, 1997, 65(1), 26 - 38 Immunization with meningococcal membrane-bound lipooligosaccharide accelerates granulocyte recovery and enhances lymphocyte proliferation in myelosuppressed mice; Quakyi EK et al.; Protective effects of detergent-treated outer membrane vesicles (D-OMVs) prepared from the parent group B M986 strain and the nonencapsulated M986-NCV mutant in myelosuppressed mice were investigated in models of experimental septic shock . The effects of D-OMVs on expansion of the myeloid compartment, on spleen cell proliferation to mitogen stimulation, and on cytokines induced during this period were investigated . On 3 consecutive days, mice were injected with 1 microgram/kg of lipooligosaccharide (LOS) or lipopolysaccharide, or 75 micrograms/kg D-OMV followed by a single dose of cyclophosphamide (200 mg/kg) 24 h later . Eight weeks after the last injection, animals were challenged with a combination of galactosamine (400 mg/kg) and live Neisseria meningitidis . More than 90% of control mice died within 24 h when challenged with 10(5) CFU of bacteria . Mice immunized with LOS or D-OMV were rendered neutropenic but were protected against bacterial challenge of at least 10(7) CFU . At different time intervals, peripheral blood samples were obtained to characterize changes in circulating blood cells . The rise in absolute granulocyte numbers occurred 24 h earlier with peak cell counts about 3 times higher than those seen in the placebo groups . Peripheral blood cells from D-OMV-treated animals expressed about twofold more Gr-1 antigen (myeloid surface cell marker) than placebo-treated controls . The proliferative responses to both B and T cells were reduced in all treatment groups due to the effects of cyclophosphamide . D-OMV treatment afforded the greatest protection for mitogen-activated lymphocytes from the lethal effects of cyclophosphamide and also enhanced T and B cell proliferation . Low IL-1 beta levels and increases in serum IL-6 were detected in all treatment groups . In contrast, significant IFN-gamma and IL-3 levels were only detected in D-OMV-treated groups . These results indicate that D-OMVs, which have reduced toxicity, have prophylactic potential in inducing specific cytokines that accelerate granulocyte recovery following cytoreductive therapy by promoting both proliferation and maturation of myeloid precursors as well as augmenting the immune system. Scand J Infect Dis, 1997, 29(2), 169 - 73 Patients with bacteremia dying before notification of positive blood cultures: a 3-year clinical study; Pedersen G et al.; In a 3-year prospective survey of bacteremia in a Danish county, 102 patients (4.6%) died before notification of positive blood cultures . Clinical records were available for 99 patients (ED group) with a male/female ratio of 1.15 and a median age of 74 years . The predominant pathogens were Escherichia coli (32%), Streptococcus pneumoniae (17%) and Staphylococcus aureus (16%) . Streptococcus pneumoniae was the only pathogen found to be more frequently in the ED group than among patients who were alive when notification was issued (ALIVE group) (17% vs 10%) . All but 2 patients with meningococcal disease had a predisposing condition . Infection was deemed to be the direct cause of death in 62%, a contributory factor in 31% and of marginal significance in 6% . Compared with the ALIVE group, the ED group was older and more frequently had a focus within the respiratory tract . Conversely, the urogenital tract and intravascular devices were less common foci . The detection time was similar for the ED and ALIVE groups (median 22 and 24 h, respectively) . 78% of ED patients had received antibiotic therapy and the coverage was appropriate in 59% . The possibility of bacteremia had not been responded to by institution of antibiotic therapy in the remaining patients . We conclude that physicians must consider antibiotic therapy when ordering sampling of blood for culture and empirical antibiotic therapy should basically provide coverage for pneumococci, S . aureus and E . coli. Neuroradiology, 1997 Jan, 39(1), 23 - 4 Bilateral white matter lesions following severe meningococcal meningoencephalitis; Muller-Jensen A et al.; Occasionally, striking abnormalities are found on MRI in patients with mild neurological disturbances . In most of these cases the diagnosis is not immediately evident and the history does not provide an unequivocal explantation . We present a patient with extensive symmetrical white matter abnormalities in the posterior temporal, temporo-occipital and parietal regions, 24 years after documented severe meningococcal meningoencephalitis . A meningitic vasculitis, affecting the insular branches of the middle cerebral arteries, could have been responsible for these changes. Acta Paediatr, 1997 Jan, 86(1), 26 - 9 Clinical data in children with meningococcal meningitis in a Spanish hospital; Luaces Cubells C et al.; Neisseria meningitidis is the main cause of bacterial meningitis in Spain . Of the 213 children included in this study with meningococcal meningitis, 7 died . Mortality was linked to a shorter time from the first symptom to diagnosis (mean time for fatal cases was 9.5 h, mean time for survivors was 19 h, p = 0.034), to deteriorated consciousness (DC) (mortality rate (MR) with DC = 6/87, MR without DC = 1/124, p = 0.02) and to shock (MR with shock = 5/7, MR without shock = 2/206, p < 0.0001) . Previous treatment reduced the yield from blood culture (36/54 versus 45/137, p < 0.0001) . Positivity in both Gram stain (GS) and cerebrospinal fluid (CSF) culture increased with longer duration of symptoms (mean GS+ = 25 h, GS- = 16 h, p = 0.004; CSF+ = 20 h, CSF- = 12 h, p = 0.001), and blood culture (BC) gave more positive results when carried out earlier (mean BC- = 14 h, BC- = 24 h, p < 0.001) . Reduced susceptibility to penicillin was seen in 34% of the strains, and rapidly evolving forms were responsible for most of the deaths; reduced susceptibility was more frequent among strains responsible for death or sequelae (9/15 = 60%) as compared with the more harmless strains (69/ 215 = 32%) (p = 0.04) . The progressive reduction of susceptibility to penicillin indicates that it should be replaced by a third-generation cephalosporine. Trans R Soc Trop Med Hyg, 1997 Jan-Feb, 91(1), 3 - 7 Meningitis outbreaks and vaccination strategy; Varaine F et al.; Three outbreaks of meningitis caused by Neisseria meningitidis serogroup A (subgroup III) are described: Niger (1991), Burundi (1992), and Guinea (1993) . These outbreaks showed unusual characteristics: a shorter inter-epidemic interval (Niger), unusual geographical location outside the meningitis belt (Burundi and Guinea), and high age-specific attack rates in all age groups (Burundi and Guinea) . Mass immunization campaigns mobilized considerable human and financial means (US $322,000 and 3000 person-days of work for health personnel to immunize 629,000 people in Guinea) . The vaccination coverage was over 80% in densely populated areas (Burundi and urban Guinea), but below 50% in less populated areas (24/27 and 26/30 sub-districts in Niger and Guinea, respectively) . The preventive fraction (proportion of cases prevented by vaccination) was substantial in Guinea (35% for a vaccine efficacy of 85%) and was higher where the campaign was initiated earlier . An 'alert' threshold indicating the onset of an epidemic of 15/100,000 cases in one week showed good sensitivity (94%), specificity (98%) and positive predictive value (89%) in Burundi, permitting quick decision making outside the meningitis belt . These 3 meningococcal meningitis outbreaks show the need for epidemic emergency preparedness and for vigilance on the whole African continent. APMIS Suppl, 1997, 68, 1 - 33 Regulator and effector functions of T-cell subsets in human Leishmania infections; Kemp M; Because of an increasing number of patients suffering from Leishmania infections and because of the serious consequences of these infections more thorough knowledge of the host factors responsible for resistance and susceptibility to the diseases is needed . In murine models of Leishmania infections the