Cent Eur J Public Health, 1995 Nov, 3(4), 189 - 94 Changing epidemiology of meningococcal invasive disease in the Czech republic caused by new clone Neisseria meningitidis C:2a:P1.2(P1.5), ET-15/37; Krizova P et al.; Invasive meningococcal disease, caused mainly by Neisseria meningitidis B, occurred only sporadically in the Czech Republic for a long period, and the use of meningococcal polysaccharide vaccine was never indicated . This situation changed in 1993, when a new meningococcal clone appeared . By means of sero/subtyping (using Whole Cell ELISA) Neisseria meningitidis C:2a:P1.2(P1.5) was quickly revealed to be the causative agent of this unusual epidemiological situation . ET typing by multilocus enzyme electrophoresis showed the prevalence of the ET-15 electrophoretic type, which belongs to the ET-37 complex . This new clone had never been identified in the Czech Republic at least since 1973 . The new clone caused an increase in the incidence of invasive meningococcal disease in the army campuses in the eastern part of the country and two local invasive meningococcal disease outbreaks in civilian population at the beginning of 1993 . In May 1993, the highest age-specific incidence in the most affected district was found in the age group of 15-19 years (52.1 per 100,000), while the respective age specific incidence for the whole Czech Republic was 1.9 per 100,000 . The vaccination campaign started in the most affected district at the beginning of June 1993 and was focused on the most affected age group, 15-19 years . After this targeted vaccination campaign the number of invasive meningococcal disease decreased in this district statistically significantly . The new clone Neisseria meningitidis C:2a:P1.2(P1.5) is causing not only a new epidemiological situation, but also a new clinical situation, characterized by more serious and frequently atypical courses of invasive meningococcal disease with a high incidence of Waterhouse-Friderichsen syndrome and meningococcal sepsis . A high fatality rate was found for the clone Neisseria meningitidis C:2a:P1.2(P1.5) (20%) compared to the "normal" fatality rate of the "non C" invasive meningococcal disease (8.8%) in 1993 . The new clone Neisseria meningitidis C:2a:P1.2(P1.5) spread between 1993 and 1995 to the whole country, nevertheless, to date no similar epidemiological situation was identified, as was that in two districts in spring 1993 . A more rapid increase in the age specific morbidity occurred recently in the age group of 1-4 years and in adult age groups as well. Mol Microbiol, 1995 Nov, 18(4), 741 - 54 Opc- and pilus-dependent interactions of meningococci with human endothelial cells: molecular mechanisms and modulation by surface polysaccharides; Virji M et al.; The interplay between four surface-expressed virulence factors of Neisseria meningitidis (pili, Opc, capsule and lipopolysaccharide (LPS)) in host cell adhesion and invasion was examined using derivatives of a serogroup B strain, MC58, created by mutation (capsule, Opc) and selection of variants . To examine the role of Opc and of additional expression of pili, bacteria lacking the expression of Opa proteins were used . The effects of different LPS structures were examined in variants expressing either sialylated (L3 immunotype) or truncated non-sialylated (L8 immunotype) LPS . Studies showed that (i) pili were essential for meningococcal interactions with host cells in both capsulate and acapsulate bacteria with the sialylated L3 LPS immunotype, (ii) the Opc-mediated invasion of host cells by piliated and non-piliated bacteria was observed only in acapsulate organisms with L8 LPS immunotype, and (iii) expression of pili in Opc-expressing bacteria resulted in increased invasion . Investigations on the mechanisms of cellular invasion indicated that the Opc-mediated invasion was dependent on the presence of serum in the incubation medium and was mediated by serum proteins with arginine-glycine-aspartic acid (RGD) sequence . Cellular invasion in piliated Opc+ phenotype also required bridging molecules containing the RGD recognition sequence and appeared to involve the integrin alpha v beta 3 as a target receptor on endothelial cells . These studies extend the previous observations on variants of a serogroup A strain (C751) and show that Opc mediates cellular invasion in distinct meningococcal strains and provide confirmation of its mechanism of action . This is the first investigation that evaluates, using derivatives of a single strain, the interplay between four meningococcal surface virulence factors in host cell invasion. Mol Microbiol, 1995 Nov, 18(3), 401 - 12 Membrane glycerophospholipid biosynthesis in Neisseria meningitidis and Neisseria gonorrhoeae: identification, characterization, and mutagenesis of a lysophosphatidic acid acyltransferase; Swartley JS et al.; Lysophosphatidic acid (LPA) acyltransferases of Neisseria meningitidis and Neisseria gonorrhoeae were identified which share homology with other prokaryotic and eukaryotic LPA acyltransferases . In Escherichia coli, the conversion of LPA to phosphatidic acid, performed by the 1-acyl-sn-glycerol-3-phosphate acyltransferase PlsC, is a critical intermediate step in the biosynthesis of membrane glycerophospholipids . A Tn916-generated mutant of a serogroup B meningococcal strain was identified that exhibited increased amounts of capsular polysaccharide, as shown by colony immunoblots, and a threefold increase in the number of assembled pili . The single, truncated 3.8 kb Tn916 insertion in the meningococcal mutant was localized within a 771 bp open reading frame, The gonococcal equivalent of this gene was identified by transformation with the cloned meningococcal mutant gene . In N . gonorrhoeae, the mutation increased piliation fivefold . The insertions were found to be within a gene that was subsequently designated nlaA (neisserial LPA acyltransferase) . The predicted neisserial LPA acyltransferases were homologous (>20% identity, >40% amino acid similarity) to the family of PlsC protein homologues . A cloned copy of the meningococcal nlaA gene complemented in trans a temperature-sensitive E . coli PlsCts- mutant . Tn916 and omega-cassette insertional inactivations of the neisserial nlaA genes altered the membrane glycerophospholipid compositions of both N . meningitidis and N . gonorrhoeae but were not lethal . Therefore, the pathogenic Neisseria spp . appear to be able to utilize alternative enzyme(s) to produce phosphatidic acid . This hypothesis is supported by the observation that, although the amounts of mature glycerophospholipids were altered in the meningococcal and the gonococcal nlaA mutants, glycerophospholipid synthesis was detectable at significant levels . In addition, acyltransferase enzymatic activity, while reduced in the gonococcal nlaA mutant, was increased in the meningococcal nlaA mutant . We postulate that the pathogenic Neisseria spp . are able to utilize alternate acyltransferases to produce glycerophospholipids in the absence of nlaA enzymatic activity . Implementation of these secondary enzymes results in alterations of glycerophospholipid composition that lead to pleiotropic effects on the cell surface components, including effects on capsule and piliation. J Infect, 1995 Nov, 31(3), 201 - 3 Rapid detection of meningococci from petechiae in acute meningococcal infection; Periappuram M et al.; In order to evaluate the diagnostic usefulness of Gram-staining films from petechial lesions in suspected meningococcal infection, data from 52 patients with confirmed infection were reviewed . Gram-negative diplococci were found in specimens from skin films in 80% (24/30) patients with petechiae . This is significantly better than results reported for Gram-staining of needle aspirates from petechiae (46%; 12/26) . Positive skin films were obtained from 89% (17/19) blood culture negative cases and 85% (17/20) CSF negative cases . In 14 cases meningococcal infection was identified only by skin films . Skin film results were not significantly affected by previous antibiotic . Gram-staining of films from petechial lesions in suspected meningococcal infection is a very rapid and effective investigation . Blood culture, CSF examination and culture, and skin films each identified meningococcal infection not identified by the other two investigations. Antimicrob Agents Chemother, 1995 Nov, 39(11), 2577 - 9 In vitro activities of ciprofloxacin, cefotaxime, ceftriaxone, chloramphenicol, and rifampin against fully susceptible and moderately penicillin-resistant Neisseria meningitidis; Blondeau JM et al.; Moderately penicillin-resistant Neisseria meningitidis was responsible for an outbreak of meningococcal disease in Saskatoon, Saskatchewan, Canada in 1993 . We tested fully susceptible and moderately resistant strains of N . meningitidis against ciprofloxacin, cefotaxime, ceftriaxone, chloramphenicol, penicillin, and rifampin . Eighteen percent of the isolates were moderately resistant to penicillin (MIC > or = 0.06 microgram/ml) whereas susceptibility was 100% for the other agents tested. Vaccine, 1995 Nov, 13(16), 1501 - 8 The antibody response to a prototype liposome vaccine containing Neisseria meningitidis outer membrane protein P1 produced in Bacillus subtilis; Idanpaan-Heikkila I et al.; Monoclonal antibodies to the class 1 outer membrane protein P1 of Neisseria meningitidis B:15:P1.7,16 have been shown to be bactericidal and protective in an infant rat meningitis model . We have produced the P1 protein in Bacillus subtilis as inclusion bodies . When the purified and denatured protein (BacP1) was reconstituted with phosphatidylcholine into liposomes, native antigenic epitopes were formed . Such liposomes were reproducibly immunogenic in mice and guinea pigs at a low dose (1-10 micrograms of BacP1 protein) and without any other adjuvant . The resulting antisera contained high titers (enzyme immunoassay) of antibodies directed to native P1 epitopes exposed on the surface of meningococcal cells . The sera were also active with live N . meningitidis in bactericidal assays and protective in the infant rat meningitis model; all these activities were specific to the serosubtype of the P1 protein. J Infect Dis, 1995 Nov, 172(5), 1273 - 8 Pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine is immunogenic in infants and children; Kayhty H et al.; Sixty-two infants and 31 toddlers were vaccinated with the tetravalent pneumococcal conjugate vaccine PncOMPC consisting of the capsular polysaccharide of pneumococcal types 6B, 14, 19F, and 23F conjugated to the outer membrane protein complex of Neisseria meningitidis . Infants were vaccinated at 2, 4, and 6 months (group A) or at 4, 6, and 14 months (group B); toddlers were vaccinated at 24 or at 24 and 26 months of age . The IgG responses to the four pneumococcal polysaccharide types were measured by EIA . In infants, types 14 and 19F induced a significant response after the first dose and types 6B and 23F after the second dose . A clearcut booster response was seen to the booster dose given at 14 months, indicating immunologic priming by the primary series at 2-6 months of age . The responses of the toddlers to one or two doses of the vaccine were very similar to the responses in infants. Clin Exp Immunol, 1995 Nov, 102(2), 290 - 6 Fulminant meningococcal septic shock in a boy with combined inherited properdin and protein C deficiency; Fijen CA et al.; A 7-year-old patient with fulminant septic shock due to Neisseria meningitidis of the uncommon serogroup Y developed extensive gangrene of the limbs . Multiple amputations were necessary and a pulmonary embolism occurred within 2 days post-operatively . Complement and haemostatic system studies, done after recovery, showed a complete absence of properdin antigen and a low protein C antigen and activity level in plasma . Defective haemolytic activity in gel by the alternative pathway of complement activation could be restored with purified properdin, indicating a properdin deficiency type 1 . Protein C antigen level as well as activity were in agreement with a protein C deficiency type I . The polymerase chain reaction (PCR) product of exon five of the protein C gene showed a substitution of 72Gly by Arg . Both deficiencies were traced among relatives of the patient . Serum of the father of the patient's mother was also properdin-deficient . Microsatellite haplotyping of the X-chromosome of the patient and his relatives showed that a distinct haplotype cosegregated with the properdin deficiency (Lodscore 2.25; four informative meioses) . The protein C type I deficiency was present in the patient's mother and her mother and cosegregated with the mutation found . So far as is known, this is the first patient described with combined inherited properdin deficiency and protein C deficiency. J Med Microbiol, 1995 Nov, 43(5), 335 - 43 Antibodies to meningococcal class 1 outer-membrane protein and its variable regions in patients with systemic meningococcal disease; Idanpaan-Heikkila I et al.; Antibodies to the meningococcal serosubtype-specific P1.7,16 protein and its variable regions (VR) were analysed in 28 convalescent sera drawn 8-36 months after systemic meningococcal disease by immunoblotting and enzyme immunoassay (EIA) methods . EIA antigens were the meningococcal P1.7,16 protein, produced in Bacillus subtilis, and peptides covering its VR1 (P1.7 region) and VR2 (P1.16 region) inserted into a bacterial penicillinase protein . In the immunoblotting method, three meningococcal reference strains were used; they expressed either the P1.7,16 protein, or only its VR1 or VR2 epitopes in their class 1 proteins . Both methods showed a strong IgG response in four sera to P1.7,16 and VR2, but not to VR1; 18 sera had no or weak anti-class 1 protein activity . The six remaining sera were positive only on blots . The VR2-specific sera had 30-fold higher bactericidal activity than those with negligible P1.7,16 responses . Previous vaccination of the patients with a B:15:P1.7,16 meningococcal vaccine was associated with a strong anti-P1.7,16 and anti-VR2 booster response that declined with time . The subtype-specific antibody activity in some sera indicated colonisation after disease by meningococci with class 1 proteins different from the strain that had caused disease. N Z Med J, 1995 Oct 27, 108(1010), 437 - 42 Meningococcal disease epidemiology and control in New Zealand; Wilson N et al.; Epidemiology, surveillance and research New Zealand has a high quality surveillance system for meningococcal disease that successfully integrates notification and laboratory data . Since 1991, New Zealand has had elevated incidence rates of meningococcal disease rising to 6.2 per 100,000 population in 1994 . This represents a rate that is four times that recorded in 1989/90 . Serogroup B infection predominates and international experience suggests that these elevated rates may continue for 5 to 15 years . Rates of meningococcal disease in Maori and Pacific Islands populations were three times higher than in Europeans at 10.0 and 12.3 per 100,000 respectively in 1994 . The rates were particularly high for infants with the rate in Maori infants under 1 year reaching 120 per 100,000 . The case fatality rate at 5.3% for 1994 would appear to be relatively low by international standards . Case control studies could be used to investigate potentially modifiable primary risk factors for disease . Intensive case review studies to investigate the role of such factors as preadmission antibiotics in reducing severe outcomes may be of benefit . The Ministry of Health or research funding organisations should consider the potential value of such studies in more detail. FEMS Microbiol Lett, 1995 Oct 15, 132(3), 277 - 83 Variable sequences in a mosaic-like domain of meningococcal tbp2 encode immunoreactive epitopes; Rokbi B et al.; Transferrin-binding proteins from Neisseria meningitidis vary among different isolates . We have identified and studied a hypervariable region adjacent to the carboxyl-end of the transferrin-binding domain of the Tbp2 molecule . The tbp2 genes from six strains of N . meningitidis were cloned and sequenced in this particular region . Sequence analysis of these regions along with five other sequences available from pathogenic Neisseria showed a common organisation of seven highly variable nucleotide stretches interspersed with six conserved nucleotide stretches . The variable regions correlated with the location of immunoreactive epitopes in polyclonal antisera raised to transferrin-binding proteins identified by peptide pin technology . Sequence analysis suggested a mosaic-like organisation of the tbp2 genes . Taken together, these data suggest that the antigenic variation in this part of the protein may result from a strong host immune pressure. Clin Infect Dis, 1995 Oct, 21(4), 1023 - 5 Meningococcal endocarditis presenting as cellulitis; Lin VH et al.; We report the case of a patient with mixed connective tissue disease who presented with two very unusual manifestations of meningococcal disease, cellulitis and endocarditis, concurrently . We also review the literature concerning Neisseria meningitidis as a causative agent of cellulitis or endocarditis . While meningococcal endocarditis or cellulitis is very rare, autoimmune disease predisposes patients to meningococcal infection . Therefore, unusual infections with this organism should be considered in the differential diagnosis of fever and rash in patients with connective tissue diseases. Vaccine, 1995 Oct, 13(14), 1353 - 9 Intranasal immunization of mice against influenza with synthetic peptides anchored to proteosomes; Levi R et al.; Synthetic vaccines that are based on peptides representing immunogenic epitopes require a carrier molecule as well as an adjuvant in order to be effective . The choice of carriers or adjuvants approved for use in humans is very limited, and a considerable effort is devoted to develop new and efficient delivery systems . One of these vehicles utilizes preparations of outer membranes of meningococci, that form hydrophobic interactions, denoted proteosomes . Immunogenic proteins and peptides can be anchored to these proteosomes vesicles, which may serve as both carrier and adjuvant functions . In the present study we examined the ability of proteosomes to present epitopes of influenza, to elicit specific anti-influenza responses and to protect mice against viral challenge after intranasal immunization . Three influenza peptides were used--one corresponding to amino acid residues 91-108 of the haemagglutinin surface glycoprotein of H3 subtype, which comprises a B-cell epitope, and two from the internal nucleoprotein--a T-helper cell (Th) epitope (residues 55-69) and a cytotoxic T-lymphocyte (CTL) epitope (147-158) . Mice were immunized intranasally (i.n.) with preparations containing each of the above epitopes, or various combinations thereof . The results obtained with this system demonstrate that influenza epitopes represented by synthetic peptides anchored to a proteosome carrier elicit both humoral and cellular specific immune responses, that can lead to partial protection of the mice from viral challenge . The importance of immunizing with vaccines containing both B- and T-cell peptide epitopes was emphasized by the demonstration that such vaccines elicited longer lasting immunity and led to more effective protection against influenza viral challenge. Mol Cell Probes, 1995 Oct, 9(5), 297 - 306 Molecular typing of Neisseria meningitidis serogroup A using the polymerase chain reaction and restriction endonuclease pattern analysis; Giorgini D et al.; A new molecular typing method for identification and characterization of Neisseria meningitidis is reported . Chromosomal DNA from 20 well-documented meningococcal strains of serogroup A originating from France, Central African Republic, Sudan and Burkina Faso were amplified using the polymerase chain reaction . Primers designed in this study were located in the pilA/pilB locus which has been shown to be conserved in the genus Neisseria . The amplified fragments were subjected to restriction endonuclease analysis using three different enzymes, and the restriction endonuclease patterns obtained were compared . Clonal isolates clustered together in distinct restriction endonuclease patterns which are described in this study and coincided with electrotypes as determined by multi-locus enzyme electrophoresis . This DNA-based typing system for meningococci may be useful for epidemiological studies. J R Army Med Corps, 1995 Oct, 141(3), 169 - 71 Atrio-ventricular dissociation in meningococcal meningitis; Etherington J et al.; A case is presented of meningococcal meningitis, without septicaemia, which was associated with a transient atrio-ventricular dissociation . The need for cardiac monitoring in similar cases is discussed. Acta Paediatr, 1995 Oct, 84(10), 1137 - 42 Factors associated with fatal outcome in childhood meningococcal disease; Flaegstad T et al.; The purpose of this study was to identify factors associated with a fatal outcome in children with meningococcal disease and to design a new clinical scoring system . We reviewed the charts of all 137 children with meningococcal disease admitted alive to the University Hospital, Tromso, during the years 1977-92 . Twelve of the children died (8.7%) . On admission the following clinical signs were significantly associated with poor outcome: peripheral vasoconstriction, cyanosis, extensive petechiae, hypotension, altered consciousness, hyperventilation and absence of neck rigidity . The laboratory parameters low pH, low base excess, thrombocytopenia, low Trombotest and leukopenia were also associated with later death . Multiple logistic regression was performed to examine the independent effect of each variable . Cyanosis, peripheral vasoconstriction and base excess < -10 mmol/l or pH < 7.35 were significantly associated with a fatal outcome . A clinical scoring system based on the extent of petechiae, the presence of peripheral vasoconstriction, hyperventilation and/or cyanosis, the absence of neck rigidity and impairment of consciousness is proposed . Twenty-nine patients received > or = 3.5 points, of whom 12 died and 12 survived . None of the patients who died had less than 3.5 points . The clinical scoring system is based solely on clinical signs . It can be done rapidly and performs well in identifying children who might benefit from early intensive care. Turk J Pediatr, 1995 Oct-Dec, 37(4), 407 - 10 Endophthalmitis in a young child with meningococcal meningitis; Aydin M et al.; Meningococcic meningitis is still a serious infection with high rates of morbidity and mortality . It is associated with severe complications . In recent years ocular complications have occurred less frequently, and endophthalmitis has been recognized as a rare complication . We present a case of meningococcic meningitis complicated by endophthalmitis. Int J Epidemiol, 1995 Oct, 24(5), 1050 - 7 Assessment of the direct effectiveness of BC meningococcal vaccine in Rio de Janeiro, Brazil: a case-control study; Noronha CP et al.; BACKGROUND . Meningococcal disease is still a serious public health problem in many countries . A vaccine produced by Cuba was the first product against B meningococcus available on a large scale . In an attempt to control the increasing incidence of this serogroup in greater Rio de Janeiro, Brazil, the vaccine was used in 1990 in children aged 6 months-9 years . About 1.6 million children were vaccinated . METHODS . In order to assess the direct effectiveness of the vaccine in preventing disease, we conducted a case-control study during the first year after vaccination . Using a hospital-based census, we selected all children hospitalized with meningococcal disease and sampled the control group among children hospitalized with other types of meningitis . Vaccine effectiveness was estimated from the relationship, 1-OR, where OR (odds ratio) was the exponential of the logistic regression coefficient for the association between meningococcal disease and previous vaccination . RESULTS . A total of 275 cases and 279 controls were selected between September 1990 and October 1991 . The summary adjusted measure of protection against serogroup B was 54% (95% confidence interval {CI}: 20-74%) . Estimated protection varied among different age strata and place of residence, being high among children aged > or = 4 years, 71% (95% CI: 34-87%), and among those who lived in the City of Rio de Janeiro, 74% (95% CI: 42-89%) . CONCLUSIONS . The results suggest that the vaccine produced by Cuba may offer protection against serogroup B meningococcal disease, but its effects may not be homogeneousPIP: Meningococcal disease is still a serious public health problem in many countries . A vaccine produced by Cuba was the first product against B meningococcus available on a large scale . In an attempt to control the increasing incidence of this serogroup in greater Rio de Janeiro, Brazil, the vaccine was used in 1990 in children 6 months-9 years old . About 1.6 million children were vaccinated . In order to assess the direct effectiveness of the vaccine in preventing disease, a case-control study was conducted during the first year after vaccination . Using a hospital-based census, all children hospitalized with meningococcal disease caused by Neisseria meningitidis were selected, and the control group came from children hospitalized with other types of meningitis at the Sao Sebastiao State Infectology Institute . Vaccine effectiveness was estimated, using ordinary logistic regression, from the relationship, 1 - OR, where OR (odds ratio) was the exponential of the logistic regression coefficient for the association between meningococcal disease and previous vaccination . A total of 275 cases and 279 controls were selected between September 1990 and October 1991 . 57% of the total cases belonged to serogroup B and 7% to serogroup C . The case fatality rate was 11% . Of the 279 controls, 46% were related to viral meningitis, 34% were related to meningitis caused by bacteria other than N . meningitidis, 13% were related to postmumps meningitis, 5% to tuberculosis meningitis, and 2% to other diseases . The summary-adjusted measure of protection against serogroup B was 54% (95% confidence interval {CI}: 20-74%) . The combined vaccine effectiveness for 230 cases and 232 controls amounted to 58% (95% CI: 31-74%) . Estimated protection varied among different age strata and place of residence, being high among children or= 4 years old, 71% (95% CI: 34-87%), and among those who lived in the City of Rio de Janeiro, 74%, (95% CI: 42-89%) . The results suggest that the vaccine produced by Cuba may offer protection against serogroup B meningococcal disease, but its effects may not be homogeneous . Br J Haematol, 1995 Oct, 91(2), 394 - 402 Serum concentrations of E-selectin, P-selectin, ICAM-1 and interleukin 6 in acute leukaemia patients with chemotherapy-induced leucopenia and bacterial infections; Bruserud O et al.; Serum concentrations of E-selectin (CD62E), P-selectin (CD62P), ICAM-1 (CD54) and interleukin 6 were investigated in acute leukaemia patients with chemotherapy-induced leucopenia and complicating bacterial infections . Serum concentrations of both E-selectin and P-selectin were decreased in the leucopenic patients without infections when compared with levels before chemotherapy; and serum concentrations of both E-selectin and P-selectin showed a further decrease during complicating bacterial infections . In contrast to the leukaemia patients, previously healthy individuals with meningococcal disease showed markedly elevated serum concentrations of E-selectin and normal levels of P-selectin during infection . Serum concentrations of ICAM-1 and interleukin 6 increased during bacterial infections in the acute leukaemia patients with chemotherapy-induced leucopenia . The alterations in serum concentrations of soluble adhesion molecules and interleukin 6 reversed when clinical signs of bacterial infections resolved during antibiotic therapy . Our results demonstrate that acute leukaemia patients with chemotherapy-induced cytopenia show altered levels of both soluble adhesion molecules and interleukin 6 during complicating bacterial infections. Protein Expr Purif, 1995 Oct, 6(5), 570 - 8 Production of lipidated meningococcal transferrin binding protein 2 in Escherichia coli; Legrain M et al.; Neisseria meningitidis strains grown under iron starvation conditions produce transferrin binding proteins (Tbp1 and Tbp2) which have been shown to play a major role in iron acquisition . Recent studies performed with Tbp2 purified from N . meningitidis suggest that this surface protein is a potential vaccine component . In order to further evaluate the immunogenicity of Tbp2, it was essential to develop a heterologous expression system to generate high amounts of purified protein . Tbp2 is produced in Neisseria as a precursor with a signal peptide whose cleavage follows a lipidation step on a cysteine residue which is the first amino acid in the mature protein . When produced in Escherichia coli with its natural signal peptide, a high amount of Tbp2 (about 10% of total cell proteins) was detected . However, most of the protein was nonlipidated precursor and only a small fraction was mature Tbp2 . In order to optimize the maturation of the precursor, the natural signal sequence was replaced by several E . coli lipoprotein signal peptides . Expression levels and maturation of the precursor were highly variable depending on the signal peptide used . With one of these, an efficient maturation and a high amount of mature lipidated Tbp2 were obtained (about 3% of total cell proteins) . A large-scale production process was then established for this E . coli-produced Tbp2. Br J Gen Pract, 1995 Oct, 45(399), 557 - 60 Clinical practice and medical research: bridging the divide between the two cultures; Owen P; The failure of the results of many research studies to be integrated into everyday clinical practice is both well documented and much decried . In the writings on why medical research and clinical practice have remained separate cultures, two issues have not been sufficiently debated . First, are medical researchers addressing the problems that cause clinicians the most concern in their consultations with patients, and secondly, are the results of research studies being presented in a manner that clinicians can both understand and use? This discussion paper highlights primary care clinicians' urgent need for information on the predictive value of the symptoms and signs seen in everyday clinical practice . Medical research has still to provide this information, often leaving general practitioners with inadequate predictive information on which to make early diagnoses, for example, on whether a patient with chest pain has a pulmonary embolus, or a child with pyrexia and rash has meningococcal septicaemia . The format in which research information is commonly presented is discussed; it has been shown that epidemiological terms used in studies are impenetrable to most clinicians . Additional ways of framing research information need to be devised that present such research information in a narrative format and numerical format, emphasizing the effects of management decisions as well as diagnostic categories, and for use in individual consultations as well as describing populations . Only then will clinicians be able to integrate into their everyday clinical practice the potentially valuable information provided by medical research. Presse Med, 1995 Sep 30, 24(28), 1305 - 7 {Partial properdin deficiency revealed by a septicemia caused by Neisseria meningitidis}; Fremeaux-Bacchi V et al.; Properdin is one of the regulatory proteins of the alternative pathway of the complement system . Human properdin deficiency is an X-linked disorder strongly predisposing to meningococcal disease . Total deficiency (type I), partial deficiency (type II), and deficiency due to a dysfunctional molecule (type III) can be differentiated immunochemically . Four males in a family showed a selective partial deficiency of properdin . These individuals had 10% of normal properdin concentration in plasma, as measured by ELISA, while the other complement components were normal . Two of the properdin-deficient individuals in two generations had meningococcal infections . Two were clinically healthy at the time of investigation . Measurement of plasma levels of properdin has to be performed in the case of Neisseria meningitidis, especially where there is a previous history of severe bacterial infections in the same family as measurement of CH50 activity is ineffective for screening properdin deficiency. Mol Microbiol, 1995 Sep, 17(6), 1201 - 14 Meningococcal pilin: a glycoprotein substituted with digalactosyl 2,4-diacetamido-2,4,6-trideoxyhexose; Stimson E et al.; Neisseria meningitidis pili are filamentous protein structures that are essential adhesins in capsulate bacteria . Pili of adhesion variants of meningococcal strain C311 contain glycosyl residues on pilin (PilE), their major structural subunit . Despite the presence of three potential N-linked glycosylation sites, none appears to be occupied in these pilins . Instead, a novel O-linked trisaccharide substituent, not previously found as a constituent of glycoproteins, is present within a peptide spanning amino acid residues 45 to 73 of the PilE molecule . This structure contains a terminal 1-4-linked digalactose moiety covalently linked to a 2,4-diacetamido-2,4,6-trideoxyhexose sugar which is directly attached to pilin . Pilins derived from galactose epimerase (galE) mutants lack the digalactosyl moiety, but retain the diacetamidotrideoxyhexose substitution . Both parental (#3) pilins and those derived from a hyper-adherent variant (#16) contained identical sugar substitutions in this region of pilin, and galE mutants of #3 were similar to the parental phenotype in their adherence to host cells . These studies have confirmed our previous observations that meningococcal pili are glycosylated and provided the first structural evidence for the presence of covalently linked carbohydrate on pili . In addition, they have revealed a completely novel protein/saccharide linkage. Gac Sanit, 1995 Sep-Oct, 9(50), 295 - 301 {Epidemiologic surveillance system for reportable diseases at the hospital}; Martinez JL et al.; The aim of this work is to present a detection system of reportable diseases among patients attending a teaching hospital . Since January 1988, based on daily data obtained from the Admissions Department of Hospital Clinic of Barcelona (HCP) (emergency department visits and hospital admissions and discharges), the Preventive Medicine Unit identifies every day those diseases considered as reportable by the Department of Health of Catalonia, Spain . Reported cases from HCP during the 1988-1991 period were compared to cases reported from HCP in 1987, as well to the corresponding cases in the remaining hospitals of Barcelona . Between 1987 and 1988 there was a 245% increase in the reporting of Individualized Reportable Diseases and of 4345% for Numeric Reportable Diseases . The increased notification has also been shown for the most frequent Individualized Reportable Diseases: 364% for hepatitis, 195% for meningococcal infection and 233% for pulmonary tuberculosis . This system is an approach to the introduction, development and perfection of the detection process, in order to improve reporting levels in the hospital, contributing to strengthen the epidemiologic surveillance system in the community. Eur J Pediatr, 1995 Sep, 154(9), 735 - 8 Inherited complement deficiency in children surviving fulminant meningococcal septic shock; Derkx HH et al.; We evaluated the complement system in 29 children (mean age: 4.5 years) who survived fulminant meningococcal septic shock . No terminal complement deficiencies were found . One patient, who experienced the most dramatic disease course, had a decreased haemolytic activity in the haemolysis-in-gel test for the alternative pathway . The properdin concentration in serum of this patient was < 0.1 microgram/ml (n = 17.1-27.7 micrograms/ml) . Coagulation studies revealed a heterozygeous type I protein C deficiency as well . He was the only patient with a Neisseria meningitidis group Y infection . CONCLUSION: Fulminant meningococcal disease due to uncommon serogroups should lead to screening of the alternative pathway of complement activation. Braz J Med Biol Res, 1995 Sep, 28(9), 981 - 9 Antibody response after immunization of Brazilian children with serogroup C meningococcal polysaccharide noncovalently complexed with outer membrane proteins; Milagres LG et al.; We have studied the antibody response of Brazilian vaccinees to C meningococcal polysaccharide (C-PS) after one or two doses of a vaccine composed of C-PS, outer membrane proteins of B meningococci and aluminum hydroxide . Total IgG, IgG1 and IgG2 as well as bactericidal activity mediated by complement were measured in serum samples from children 3 to 83 months of age (post-vaccination IgG, IgG1 and IgG2 levels of 2.4 to 13.4 micrograms/ml; less than 18 to 67.8 U/ml and less than 18 to 106.8 U/ml, respectively) and from individuals 10 to 14 years of age (post-vaccination IgG, IgG1 and IgG2 levels of 14.6 micrograms/ml, 23.7 U/ml and 112.0 U/ml, respectively) . The antibody response, measured as IgG levels, was age-dependent . Although high antibody levels were demonstrable by enzyme-linked immunosorbent assay (ELISA), bactericidal activity was not demonstrable (less than 1:4) in serum from children aged less than 24 months . A significant bactericidal activity was detected in serum of children older than 49 months of age and in individuals 10 to 14 years of age . A predominance of IgG2 was observed in post-vaccination serum samples from children belonging to those two age groups . The antibody concentration sufficient to confer protection as well as the possible causes of the poor correlation observed between ELISA and bactericidal activity results are discussed. Vaccine, 1995 Sep, 13(13), 1207 - 12 Human antibody response to meningococcal transferrin binding proteins: evidence for vaccine potential; Gorringe AR et al.; During iron-limited growth Neisseria meningitidis expresses two transferrin binding proteins, TBP1 and TBP2, with molecular masses of approximately 98 and 65-90 kDa depending on strain . Mixtures of TBP1 and TBP2 (TBP1 + 2) from three meningococcal strains were purified using affinity chromatography and used to determine anti-TBP antibodies in human sera by ELISA . Sera were obtained from healthy individuals, asymptomatic carriers of N . meningitidis and cases of meningococcal disease . Healthy individuals had little detectable antibody to TBPs but sera from carriers and cases exhibited a response demonstrating that TBPs are expressed in vivo during both carriage and disease . The ELISA absorbances produced by each of the individual sera to TBPs from the three meningococcal strains were compared and very high correlation coefficients were obtained, indicating that human anti-TBP antibodies, in contrast to mouse and rabbit antibodies, are cross-reactive between strains . Antibodies to separately purified TBP1 and TBP2 were also detected in both cases and carriers . The IgG and IgM response to TBP1 + 2 was greater in cases than carriers but the mean IgA response was the same . This demonstration of an antibody response that is cross-reactive between TBP types greatly strengthens the case for inclusion of TBPs in a meningococcal vaccine to protect against all serogroups and serotypes. Pediatr Infect Dis J, 1995 Sep, 14(9), 797 - 803 The antimeningococcal vaccine VAMENGOC B-C induced poor serum and salivary antibody response in young Brazilian children; Carbonare SB et al.; In 1989 about 2.3 million Brazilian children received the antimeningococcal vaccine VAMENGOC B-C (Havana, Cuba) . We evaluated the serum and secretory immune response of vaccinated children by enzyme-linked immunosorbent assay with outer membrane complex antigens . Western blotting and bacterial adherence inhibition assays with human buccal epithelial cells were performed with some of the samples . Serum and salivary antibody concentrations to Neisseria meningitidis Group B of vaccinated children < 4 years old were not significantly higher than those of nonvaccinated children, as observed in convalescing patients used as positive controls . Older children (4 to 6 years old) presented a slight increase in antibody OD indexes . Sera and saliva from vaccinated children showed a weak reaction with meningococcal antigen by Western blotting and were unable to inhibit significantly the adherence of N . meningitidis B to buccal epithelial cells . These data suggest that this vaccine induced a poor serum and salivary antibody response in the population studied. Microb Pathog, 1995 Sep, 19(3), 159 - 68 Short-chain lipopolysaccharide mutants of serogroup B Neisseria meningitidis of potential value for production of outer membrane vesicle vaccines; Andersen SR et al.; Four lipopolysaccharide (LPS) mutants (Mu-1 to Mu-4) were isolated after exposing Neisseria meningitidis strain 44/76 to pyocins from Pseudomonas aeruginosa . Parent strain LPS contained one major SDS-PAGE band expressing the immunotype determinants of L3, L3,7 and L3,7,9 and a minor band of higher mobility expressing the immunotype determinants of L8, L8a, L1,8,10 and L11 . Each mutant LPS appeared as one SDS-PAGE band of higher mobility than the bands of the parent strain . None of these LPSs expressed the immunotype determinants of the parent strain, except Mu-4 LPS which reacted with the L11-specific MAb 4C4 . Strain 44/76 LPS was found to contain galactose (Gal), glucose (Glc), heptose (Hep), glucosamine (GlcN), and 2-keto-3-deoxy-octulosonic acid (Kdo) in the molar ratios of 1.9:1.3:1.7:3.5:2.1 . The corresponding ratios of the mutants were: Mu-4, 0:1.7:1.7:2.8:2.0; Mu-3, 0:0:1.7:2.4:1.6; Mu-2, 0:0:2.1:1.8:2.0, Mu-1, 0:0:1.8:1.9 . Thus, all mutant LPSs lacked Gal and possessed less GlcN as compared to strain 44/76 LPS . Consequently, these mutants do not express the lacto-N-neo-tetraose (Gal1-4GlcN1-3Gal1-4Glc) commonly found as a part of meningococcal LPS and also on structures of human erythrocytes . These LPS mutants will be considered for use in production of OMV vaccines without host-like antigens, which might favour induction of antibodies to more conserved epitopes of meningococcal LPS. Clin Diagn Lab Immunol, 1995 Sep, 2(5), 574 - 82 Antibody responses to the capsular polysaccharide of Neisseria meningitidis serogroup B in patients with meningococcal disease; Granoff DM et al.; We measured antibody responses to meningococcal serogroup B (MenB) polysaccharide (PS) by enzyme-linked immunosorbent assay (ELISA) in sera from 94 patients from The Netherlands with disease caused by Neisseria meningitidis group B . The patients ranged in age from 3 to 73 years (mean age, 18.8 years) . In initial studies we showed that the binding of a panel of MenB PS-reactive human immunoglobulin M (IgM) paraproteins to biotinylated MenB PS bound to avidin-coated microtiter wells was inhibited > 90% by the addition of soluble MenB PS or encapsulated group B meningococci . In contrast, inhibition of IgM anti-MenB PS antibody-binding activity in many of the patient sera was less than 50% (range, 20 to 94%) . These data suggested a high frequency of nonspecific binding in the patient sera . Therefore, all serum samples were assayed in replicate in the presence or absence of soluble MenB PS, and only the inhibitable fraction of the binding signal was used to calculate the anti-MenB PS antibody concentrations . In 17 control patients with meningococcal disease caused by serogroup A or C strains, there was no significant difference in the respective IgM or IgG anti-MenB PS antibody concentrations in paired acute- and convalescent-phase sera . In contrast, in patients with MenB disease, the geometric mean IgM anti-MenB PS antibody concentration increased from 3.9 units/ml in acute-phase serum to 10.5 units/ml in convalescent-phase serum (P < 0.001) . The corresponding geometric mean IgG anti-MenB PS antibody titers were 1:27 and 1:36 (P < 0.05) . There was only a weak relationship between age and the magnitude of the logarithm of the antibody concentrations in convalescent-phase sera (for IgM, r2 = 0.06 and P < 0.05; for IgG, r2 = 0.08 and P < 0.01) . Our data indicate that precautions are needed to avoid nonspecificity in measuring serum antibody responses to MenB PS by ELISA . Furthermore, although this PS is thought to be a poor immunogen, patients as young as 3 years of age recovering from MenB disease demonstrate both ImG and IgG antibody responses in serum. Genomics, 1995 Sep 1, 29(1), 1 - 8 Sequence-based analysis of properdin deficiency: identification of point mutations in two phenotypic forms of an X-linked immunodeficiency; Westberg J et al.; Properdin deficiency is an inherited X-linked disorder causing increased susceptibility to meningococcal disease . Here, underlying genetic defects in the properdin gene were identified for the first time . Samples from individuals with type I deficiency, defined as complete absence of properdin in serum, and individuals with type II deficiency, characterized by low concentrations of properdin in serum, were analyzed by direct chromosome sequencing of overlapping PCR products . The complete gene, including 10 exons and 9 introns, covering 6460 bases of the region Xp11, was investigated by direct solid-phase sequencing . In the related individuals with type I deficiency a C to T mutation in exon 5 was identified, which gives rise to a stop codon TGA and thus a truncated gene product . In addition, point mutations were found in 4 introns and a silent mutation in exon 10 . In the properdin gene from related individuals with type II deficiency two point mutations were found, one in intron 3 and one in exon 4 . The latter mutation yields a substitution of arginine to tryptophan, which may affect folding, secretion, and/or turnover of the protein . The genetic and biochemical implications of these mutations are discussed. Zh Mikrobiol Epidemiol Immunobiol, 1995 Sep-Oct, (5), 41 - 4 {The serosubtyping of serogroup B meningococci}; Koroleva IS et al.; The results of the study of 116 Neisseria meningitidis strains, isolated from patients at different territories of Russia at the period of 1983-1992, by the method of the enzyme immunoassay are presented . 13.8 +/- 3.2% of the strains were found to have stereotype proteins and 59.5 +/- 4.5%, subtype proteins . In the population of circulating meningococcal strains no absolute prevalence of any single serotype or subtype was established . The comparison of the tendency in the course of morbidity rate and the state of the serosubtype composition of isolated group B N . meningitidis stains is indicative of the favorable situation with respect to meningococcal infection and the importance of further observation of the circulating strains. Zh Mikrobiol Epidemiol Immunobiol, 1995 Sep-Oct, (5), 30 - 2 {The ontogeny of the cell receptors of the adhesion of meningococci and influenza viruses}; Rumiantsev SN et al.; Specific age and individual features of the adhesion of Neisseria meningitidis, groups A, B and C, and influenza viruses, types A and B, to red blood cells of humans aged 0-60 years were studied . The study revealed that the red blood cells of newborns, in contrast to those of persons of older age groups, are highly resistant to N . meningitidis adhesion, but highly sensitive to the adhesion of influenza viruses, though to a varying degree . The postnatal period of ontogenesis is characterized first by a sharp rise (up to 1 month) and then by a slower increase of the individual sensitivity of red blood cells to N.meningitidis adhesion without essential changes in the sensitivity of the same cells to the adhesion of influenza viruses. Infect Immun, 1995 Sep, 63(9), 3531 - 6 Comparison among opsonic activity, antimeningococcal immunoglobulin G response, and serum bactericidal activity against meningococci in sera from vaccinees after immunization with a serogroup B outer membrane vesicle vaccine; Aase A et al.; Opsonic activity in sera from 27 military recruits vaccinated with the Norwegian meningococcal serogroup B outer membrane vesicle vaccine was measured as respiratory burst with polymorphonuclear leukocytes as the effector cells and meningococci of the epidemic strain as the target . The results were compared with antimeningococcal IgG antibodies against an outer membrane vesicle coat in an enzyme-linked immunosorbent assay and with serum bactericidal activity . The vaccinees were immunized twice, with a 6-week interval between the two . The serum samples studied were collected at day zero, after 6 weeks, and after 12 weeks . Both serum bactericidal activity and respiratory burst were measured by adding external serum as the complement source . The results revealed a significant increase in specific IgG response, serum bactericidal activity, and respiratory burst after vaccination . We found a highly significant correlation between the responses in all three assays (P < 0.0001) . The highest correlation was found between respiratory burst and antimeningococcal IgG response (r = 0.93) . This result strongly indicates that respiratory burst is mediated almost exclusively by IgG antibodies . The correlation between antimeningococcal IgG response and serum bactericidal activity was slightly lower (r = 0.83) . The correlation between respiratory burst and serum bactericidal activity was further reduced (r = 0.78), and some of the sera revealed a marked preference for only one of the activities . This result means that respiratory burst and serum bactericidal activity in part are induced by different mediators, and to obtain a more complete picture of the potential protective activity, both assays should be applied to survey a vaccine trial. Eur J Immunol, 1995 Sep, 25(9), 2714 - 7 Polymorphonuclear granulocytes enhance lipopolysaccharide-induced soluble p75 tumor necrosis factor receptor release from mononuclear cells; Lien E et al.; Lipopolysaccharide (LPS), a part of the Gram-negative bacteria cell wall, is a potent inducer of tumor necrosis factor (TNF) . TNF is an important mediator in Gram-negative infections such as meningococcal septic shock, but its harmful action can be prevented by the natural occurring soluble (s) TNF receptors (sTNFR) sp55 and sp75 . In this study, the effect of LPS on release of sTNFR was investigated . First, we found a selective increase in human whole-blood sp75 TNFR levels following LPS stimulation, accompanied by no increase in sp55 . Separating the different blood cell populations, mononuclear cells (PBMC) selectively released sp75 upon LPS stimulation, while LPS induced a minor increase in sp75 release from polymorphonuclear granulocytes . Interestingly, in co-cultures of PBMC and granulocytes, the release of LPS-induced sp75 TNFR was enhanced . Second, adherent monocytes were also found to selectively release sp75 TNFR upon LPS stimulation, where Neisseria meningitidis LPS was found to be 100-1000 times more potent in inducing sp75 release than Escherichia coli LPS . Using flow cytometry, the monocyte membrane distribution of both TNFR were found to be increased after LPS stimulation . Third, human umbilical vein endothelial cells selectively released sp55 TNFR after stimulation with LPS . We conclude that mononuclear and endothelial cells might be the main sources of soluble p75 and p55 TNFR, respectively, observed in Gram-negative sepsis, although these receptors are released in vivo more rapidly than they are in vitro. Am J Phys Med Rehabil, 1995 Sep-Oct, 74(5), 375 - 9 Neurologic recovery and functional improvement after vecuronium-induced quadriparesis; Munin MC et al.; Vecuronium bromide (Norcuron, Organon, Inc., West Orange, NJ) is a common neuromuscular blocking agent used to facilitate mechanical ventilation . Cases have been reported in which prolonged use of vecuronium resulted in severe motor neuropathy, with or without myopathy . However, the time course of recovery, the functional prognosis, and the use of inpatient rehabilitation is not well-established . We are reporting the functional recovery of two cases with the diagnosis of severe vecuronium motor neuropathy and/or myopathy . The patients presented with pneumonia and meningococcemia, respectively, and received vecuronium during ventilatory support, which lead to quadriparesis . In one patient, vecuronium toxicity occurred while neuromuscular junction monitoring was in place . Significant improvement was noted during an average of 3 to 4 wk in a comprehensive inpatient rehabilitation program, documented by the improvement in total motor Functional Independence Measure scores for patient 1 (from 15 to 71) and for patient 2 (from 65 to 84) . In addition, the distal compound motor amplitudes showed a 4-fold increase for the ulnar, a 7-fold increase for the median, an 11-fold increase for the peroneal, and a 3-fold increase for the tibial nerves on follow-up nerve conduction studies correlating with neurologic recovery . In summary, even when patients present with quadriparesis, the recovery after vecuronium toxicity appears to be favorable. Orthop Nurs, 1995 Sep-Oct, 14(5), 9 - 15; quiz 16-7 Skeletal and cutaneous sequelae to meningococcal purpura; Williamson V et al.; Meningococcal infection can produce symptoms that have severe morbid or even fatal effects . The survival rate has increased over the last 20 years and health care workers are now faced with managing the sequelae of cutaneous and skeletal necroses . It is important for nurses to recognize symptoms of the disease as well as associated complications . A multidisciplinary approach is needed to manage all phases of the illness . This phenomenon occurs most commonly in children but may be seen in adolescents and young adults as well . Despite extensive alteration in body image and the need for long-term rehabilitation, with proper management, a full recovery may be expected. Infect Immun, 1995 Sep, 63(9), 3473 - 8 Conjugates of synthetic cyclic peptides elicit bactericidal antibodies against a conformational epitope on a class 1 outer membrane protein of Neisseria meningitidis; Hoogerhout P et al.; Bactericidal antibodies directed against surface loops of class 1 outer membrane proteins play a crucial role in protection against meningitis and sepsis caused by Neisseria meningitidis . So far, all efforts to obtain protective antibodies against these apparently conformational epitopes by using linear peptide analogs have been in vain . In this study, conjugates of head-to-tail cyclic peptides encompassing the predicted top of a protective surface loop were used for immunization . A series of 18 cyclic peptides with a ring size ranging from 7 to 17 residues, conjugated to tetanus toxoid, was investigated . Antipeptide and anti-whole-cell immunoglobulin G (IgG) titers elicited by the conjugates were determined . Conjugates of three peptides, containing 14, 15, and 17 amino acid residues (peptides 7, 12, and 13, respectively), induced an anti-whole-cell titer when Quillaja saponin A was used as the adjuvant . When alum was used as the adjuvant, the conjugate of peptide 12 did not elicit an anti-whole-cell response . From the Quillaja saponin A group, some of the sera obtained with conjugates of peptides 7 and 12 and all sera obtained with the peptide 13 conjugate were bactericidal in vitro . None of the sera evoked with alum as the adjuvant showed bactericidal activity . Nonbactericidal sera contained IgG1 primarily, whereas bactericidal sera showed significant titers of IgG2a and IgG2b . Class 1 protein-derived synthetic cyclic peptides which are capable of eliciting bactericidal antibodies, such as peptide 13 derived from meningococcal strain H44/76, represent potential candidates for a (semi)synthetic vaccine against meningococcal disease. Commun Dis Rep CDR Rev, 1995 Aug 18, 5(9), R135 - 7 Early management of meningococcal disease; Woodward CM et al.; Sixty-eight cases of meningococcal disease were ascertained at a district hospital in Wessex region over a four year period . Forty-seven of the 68 patients were reported to have a haemorrhagic rash on admission to hospital, three of whom died . Twelve of the 47 had received parenteral antibiotic treatment before admission, and none of these died . The overall case fatality was 4% (3/68) . Sixty-three patients were referred by general practitioners . In 19 of the 63 a haemorrhagic rash was described at referral, and a haemorrhagic rash was described in 42 on hospital admission . Thirteen of the 63 received parenteral antibiotic treatment before admission . Such treatment was significantly more likely when the referral letter described a haemorrhagic rash and appeared to be less likely in child cases and when patients had received earlier oral antibiotics. Commun Dis Rep CDR Rev, 1995 Aug 18, 5(9), R130 - 5 Meningococcal vaccines for the United Kingdom; Herbert MA et al.; New meningococcal vaccines are needed in the United Kingdom with some urgency . Almost all Neisseria meningitidis disease in this country is caused by serogroups B and C . Infants have the highest attack rates, but also make the poorest immunological responses to potential vaccines . The development of vaccines that protect infants is a significant challenge . A capsule-based serogroup B vaccine is unlikely to be successful in infants because the capsule is poorly immunogenic and the polysaccharide molecule mimics a human epitope . Without completely discounting capsule as an immunogen, alternate antigens are being considered for immunisation: outer membrane proteins (OMP), iron regulating proteins, and lipopolysaccharide . Vaccines based on OMP have been used in several phase 3 trials in South Africa, Cuba, Brazil, Norway, and Chile, in which two doses of vaccine were given . The Cuban and Norwegian vaccines have been compared in phase 2 trials in Iceland and Chile . Potential limitations are epitope heterogeneity and the theoretical ability of N . meningitidis to adapt even to hosts who have received polyvalent vaccines . A phase 2 trial of a hexavalent class 1 OMP vaccine is under way in Gloucester, with 100 babies receiving injections at 2, 3, and 4 months . Serogroup C vaccines have been developed from capsular polysaccharide but, unconjugated, these vaccines do not protect those under 2 years of age . Conjugate vaccines with C and AC polysaccharides are immunogenic in infants, but antibody titres may wane quickly.(ABSTRACT TRUNCATED AT 250 WORDS) Commun Dis Rep CDR Rev, 1995 Aug 18, 5(9), R125 - 30 Meningococcal infections in England and Wales: 1994; Jones DM et al.; One thousand one hundred and twenty-nine isolates of Neisseria meningitidis from cases of invasive disease were submitted to the PHLS Meningococcal Reference Unit in 1994, a fall of 13% from the total of 1297 in 1993 . One hundred and seventy-four cases were diagnosed serologically, making 1303 laboratory ascertained cases, compared with 1368 in 1993 . The overall fall of 4% was similar to the 5% fall in notifications to the Office of Population Censuses and Surveys . The seasonal increase between the third and fourth quarters of the year was less apparent than usual in 1994, when a higher proportion of cases occurred during the summer months . Regional rates of infection varied, notably in the proportions of group C infections, which were highest in the south east . DNA based typing techniques have clarified the characterisation of previously non-typable organisms . B4PI.4 has been identified as a recently emergent strain, which is now responsible for a quarter of all group B infections . Considerable regional variation was observed in the use of serodiagnosis . The monthly distribution of cases diagnosed serologically was similar to that of cases confirmed by isolation, but the age profile was skewed towards older patients. N Z Med J, 1995 Aug 11, 108(1005), 318 - 9 Assessment of the risk of transmission of N meningitidis in a classroom setting; Eberhart-Phillips J et al.; AIM . To evaluate the risk of colonisation with N meningitidis among university classroom contacts of a student with invasive meningococcal disease . METHODS . Throat cultures were obtained from classmates and faculty exposed to a university student with meningococcal disease . Exposures to the index case were quantified using a questionnaire . RESULTS . None of the 41 students and staff from whom cultures were obtained showed evidence of colonisation with N meningitidis . The contacts had spent an average of 13.5 h in class with the index case during the 2 days prior to the onset of her illness . CONCLUSIONS . The risk of colonisation with N meningitidis among casual university classroom contacts appears to be low . This study lends support to decisions to withhold chemoprophylaxis in most instances of such contact. Ugeskr Laeger, 1995 Aug 7, 157(32), 4454 - 8 {Outbreak of serogroup C meningococcal disease among teenagers in Randers--preventive measures and examination of the meningococcal carrier conditions}; Ronne T et al.; An outbreak involving 20 cases of serogroup C meningococcal disease, predominantly among teenagers, occurred over a seven-month period in the Randers area of Denmark . The cases were caused by a serogroup C:2a:P1.2 sulphonamide-resistant strain . The available evidence was against the transmission being related to particular schools . The outbreak was experienced as three clusters . At two schools involved in the first and the third cluster of the outbreak, 351 students were examined regarding pharyngeal carriage of meningococci, 282 of whom were tested again 17 weeks later; 308 students attending two similar schools in a nearby area were examined once . The majority of strains isolated from group C carriers in the high-risk area were serologically indistinguishable from the outbreak strain (13/14 = 95%), but less often sulphonamide-resistant (5/13 = 38%) . In both areas, the overall carrier rate (30%), the overall group C rate (3%) and, the carrier rate for the outbreak strain (1%) were the same . The attack rate for the outbreak strain differed significantly: 1/40 in the high-risk area versus 1/2.500 in the normal risk area . No conditions that might explain this difference were revealed . Immediately after recognition of the first and the third cluster, 780 and 13,300 students, respectively, were vaccinated with meningococcal polysaccharide vaccine A+C . It was concluded that the definition of target groups for vaccination should be liberal, because the "at risk" population may be difficult to recognize at the onset of an outbreak. Eur J Epidemiol, 1995 Aug, 11(4), 393 - 6 Epidemiology of meningococcal infections in children in mid-southern part of Turkey; Alhan E et al.; 59 patients were treated for meningococcal infections in Cukurova University Faculty of Medicine, Division of Pediatric Infectious Diseases . 50.8% of patients were male, 33.9% were under two years of age and 61% were under five . 78% of patients were admitted to hospital in winter and spring time . Meningococcal meningitis (MM) was present in 39% of patients on admission, however, meningococcemia in 27.1% and meningococcemia and meningococcic meningitis (Meningococcemia + MM) in 33.9% . Fatality rate was 18.6% and no association was found between mortality and clinical type of disease (p > 0.05), but mortality ratio decreased with an increasing age (p < 0.01) . No deaths occurred among the 12 patients who received i.v . penicillin treatment shortly before admitting to hospital, on the other hand 11 of 47 patients (23.4%) without such a previous treatment diedPIP: The clinical and laboratory findings of 59 patients treated for meningococcal disease between January 1, 1989, and December 31, 1993, in Adana, Turkey's Cukurova University, Faculty of Medicine, Division of Pediatric Infectious Diseases were analyzed retrospectively . The diagnosis was based on clinical findings, positive blood or cerebrospinal fluid (CSF) cultures, and the presence of gram negative diplococci in the CSF and in the smears from petechiae . Of 59 patients, 29 (49.2%) were female and 30 (50.8%) were male, with ages ranging from 1 month to 14 years . 20 (33.9%) patients were in the 0-2 and 36 (61%) were in the 0-5 age group . Most of the patients (45.7%) were admitted to the hospital in the winter, followed by spring (32.2%), summer (15.3%), and fall (6.8%) . In January and February there seemed to be a peak in admission rates (18.6% and 16.9%, respectively) . The distribution of patients with respect to seasons showed a statistically significant difference (p .0001) . The overall case fatality was 18.6% (11/59) . Meningococcal meningitis (MM) was diagnosed in 23 (39%) patients, meningococcemia in 16 (27.1%), and MM + meningococcemia in 20 (33.9%) . 10 of 20 children 0-2 years of age presented with meningococcemia alone . On the other hand, 11 (47.8%) of the 23 patients over 5 years showed MM alone . Clinical presentation revealed a significant association with certain age groups (p .05) . Fatality ratios in children under 2 years old and in children 2-14 years old were 35% and 10.2%, respectively, and there was a significant trend for decreasing case fatality rate with increasing age (p .01) . All patients aged 0-3 months died . The fatality rate was the lowest among patients over 5 years of age (8.7%, 2/23) . The mortality rate did not change with clinical presentation (p .05) . Two patients (8.7%) with MM died, while this rate was 20% (4/20) in patients with MM + meningococcemia . 5 of 16 (31.3%) patients died in the group with meningococcemia only . Signs of upper respiratory tract infection were present in 11 (18.6%) patients during their initial physical examination, but no statistically significant relationship was found in respect to mortality (p .05) . Enferm Infecc Microbiol Clin, 1995 Aug-Sep, 13(7), 398 - 405 {Prevalence of Neisseria meningitidis carriers among the population of Cerdanyola (Barcelona)}; Fontanals D et al.; OBJECTIVE: To determine the prevalence of Neisseria meningitidis (N . meningitidis) from healthy carriers and its resistance to penicillin in Cerdanyola population . To asses which risk factors were associated with healthy carriers and compare some epidemiologic characteristics between people with penicillin sensitive and penicillin resistant strains . METHODS: Cross-sectional seasonal study of 1500 individuals selected from day care centers, schools, colleges, cultural and working centers, located in different areas of Cerdanyola . We performed throat smears and immediate culture onto selective media for isolation of N . meningitidis . Data were evaluated by univariate and multivariate statistical analysis using the SPSS statistical package . RESULTS: One hundred and ninety-one (12.7%) individuals harbored N . meningitidis strains . In logistic regression multivariate analysis, meningococcal carriage significantly increased for the age group 14-18 years (OR = 4.55 with respect to the reference group, 0-3 years), in the spring (OR = 2.29), male sex (OR = 1.67), and active smoking (OR = 1.45, intervals of 10 cigarettes/day), while meningococcal carriage significantly decreased in the group under 4 years at age (OR = 0.55), with prior use of antibiotics (OR = 0.58) and with bigger housing space (OR = 0.84 for 10 m2/person) . A 42% of N . meningitidis strains in carriers from this population showed decreased sensitivity to penicillin (MIC > 0.1 microgram/ml) . We have not found significantly association between the variables studied and penicillin resistance among carriers of N . meningitidis . CONCLUSIONS: Age, spring season, sex, active smoking and overcrowded housing are significantly associated to carrier state . Prior use of antibiotics decreased to carrier state . According to our findings, reducing smoking habits and improving housing conditions may be useful measures to reduce the prevalence of carriers. J Bacteriol, 1995 Aug, 177(16), 4669 - 75 Sulfonamide resistance in Neisseria meningitidis as defined by site-directed mutagenesis could have its origin in other species; Fermer C et al.; Sulfonamide resistance in Neisseria meningitidis is mediated by altered forms of the chromosomal gene for the drug target enzyme dihydropteroate synthase . Sulfonamides have been used for decades both for prophylaxis and the treatment of meningococcal disease, and resistance is common . Two types of resistance determinants have been identified, and regions important for drug insusceptibility to the corresponding enzyme have been defined by site-directed mutagenesis . Both types of resistance traits have spread among strains of N . meningitidis of different serogroups and serotypes, and the large differences at the nucleotide level in a comparison of the resistance genes with the dhps genes of susceptible meningococci indicate the origin of one or maybe both types in other Neisseria species . One sulfonamide-sensitive strain of N . meningitidis was found to have a mosaic dhps gene with a central part identical to the corresponding part of a gonococcal strain . This observation supports the idea of an interspecies transfer of genetic material in Neisseria species as a mechanism for the development of chromosomally mediated resistance. J Infect Dis, 1995 Aug, 172(2), 433 - 9 Correlation between proinflammatory cytokines and antiinflammatory mediators and the severity of disease in meningococcal infections; van Deuren M et al.; Pro- and antiinflammatory cytokines and mediators were measured in 39 patients with acute life-threatening meningococcal infections classified into 3 groups: A, meningitis without shock (n = 20); B, meningitis with shock (n = 9); and C, shock without meningitis (n = 10) . The plasma concentrations of proinflammatory endotoxin, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8 and antiinflammatory cytokines and mediators IL-1 receptor antagonist, IL-10, and soluble TNF receptors p55 and p75 were strongly associated with this classification; the highest concentrations were in group C . IL-4 was not measurable . IL-1 beta was increased only in rapidly fatal cases . In addition, cerebrospinal fluid (CSF) was analyzed in 21 patients for TNF-alpha and its soluble receptors . In CSF, these compounds were mainly increased in group A, reflecting an intrathecal compartmentalized cytokine production . It is concluded that both pro- and antiinflammatory mediators are simultaneously increased and are strongly associated with a classification based on simple clinical parameters. Infect Immun, 1995 Aug, 63(8), 2958 - 67 Characterization of lbpA, the structural gene for a lactoferrin receptor in Neisseria gonorrhoeae; Biswas GD et al.; Neisseria gonorrhoeae acquires iron (Fe) efficiently from lactoferrin (LF) . A 103-kDa gonococcal outer membrane LF-binding protein (Lbp) was identified previously . We isolated the structural gene lbpA for Lbp1 by screening a gonococcal library for a clone that could repair an LF- receptor mutant . An mTnCm3 transposon insertion mutant of lbpA was unable to use LF-bound Fe for growth, unable to bind LF to whole cells, and unable to express Lbp1 . The DNA sequence of lbpA predicted a protein that shared 94% identity with the meningococcal LF receptor protein, Lbp, and was closely related to Tbp1, one of the transferrin receptor proteins . Clinical isolates of gonococci are frequently unable to acquire Fe from LF, and LF- isolates do not have a functional LF receptor . The wild-type lbpA gene transformed most tested LF- clinical isolates to LF+, indicating that lbpA is defective in many clinical isolates. J Clin Microbiol, 1995 Aug, 33(8), 2209 - 11 Molecular epidemiology of an outbreak of meningococcal disease in a university community; Edmond MB et al.; Over a 2-month period, five cases of serogroup C meningococcal disease occurred in Iowa City, Iowa . Two patients were unacquainted university students who had independently visited another university with endemic meningococcal disease . Isolates from these patients had DNA fingerprints identical to those of the isolates responsible for infections on the other campus . Three cases for which the patients' isolates had a different DNA fingerprint were linked to visiting a local tavern . To disrupt the outbreak, the University of Iowa offered free meningococcal vaccine to all students . This report demonstrates that outbreaks of meningococcal disease may be due to more than one circulating strain and illustrates the utility of pulsed-field gel electrophoresis in defining the molecular epidemiology of meningococcal infections. Ugeskr Laeger, 1995 Jul 3, 157(27), 3909 - 10 {Primary meningococcal arthritis caused by Neisseria meningitidis . One of the many manifestations of meningococcal disease}; Christiansen JC; A case of primary meningococcal arthritis in the left hip of a nineteen year-old female is described . The diagnosis was based on microscopical detection of Gram-negative diplococci and a positive meningococcal antibody-test . Treatment with benzylpenicilline and drainage was instituted . Although she was soon asymptomatic, the X-ray examination showed a slight destruction of the hip joint . One and a half years later the X-ray findings were normal . Attention is directed to the broad clinical spectrum of meningococcal disease. Pediatr Pol, 1995 Jul, 70(7), 607 - 11 {Splenic necrosis during meningococcal sepsis treated with splenectomy}; Smolska I et al.; The authors present rare case of splenic necrosis during meningococcal sepsis in an eight-month-old infant . The diagnosis was based on ultrasonographic examination and confirmed by CT . These investigations were conducted because of splenomegaly and gastrointestinal tract disturbances . Splenectomy gave good results. Rev Inst Med Trop Sao Paulo, 1995 Jul-Aug, 37(4), 281 - 9 Genetic structure of Neisseria meningitidis serogroup C epidemic strains in south Brazil; Sacchi CT et al.; In the present study we report the results of an analysis, based on serotyping, multilocus enzyme electrophoresis (MEE), and ribotyping of N . meningitidis serogroup C strains isolated from patients with meningococcal disease (MD) in Rio Grande do Sul (RS) and Santa Catarina (SC) States, Brazil, as the Center of Epidemiology Control of Ministry of Health detected an increasing of MD cases due to this serogroup in the last two years (1992-1993) . We have demonstrated that the MD due to N.meningitidis serogroup C strains in RS and SC States occurring in the last 4 years were caused mainly by one clone of strains (ET 40), with isolates indistinguishable by serogroup, serotype, subtype and even by ribotyping . One small number of cases that were not due to an ET 40 strains, represent closely related clones that probably are new lineages generated from the ET 40 clone referred as ET 11A complex . We have also analyzed N.meningitidis serogroup C strains isolated in the greater Sao Paulo in 1976 as representative of the first post epidemic year in that region . The ribotyping method, as well as MEE, could provide useful information about the clonal characteristics of those isolates and also of strains isolated in south Brazil . The strains from 1976 have more similarity with the actual endemic than epidemic strains, by the ribotyping, sulfonamide sensitivity, and MEE results . In conclusion, serotyping with monoclonal antibodies (C:2b:P1.3), MEE (ET 11 and ET 11A complex), and ribotyping by using ClaI restriction enzyme (Rb2), were useful to characterize these epidemic strains of N.meningitidis related to the increased incidence of MD in different States of south Brazil . It is mostly probable that these N.meningitidis serogroup C strains have poor or no genetic correlation with 1971-1975 epidemic serogroup C strains . The genetic similarity of members of the ET 11 and ET 11A complex were confirmed by the ribotyping method by using three restriction endonucleases. J Infect, 1995 Jul, 31(1), 67 - 8 Recurrent meningococcal septicaemia and properdin deficiency; Cunliffe NA et al.; A 32-year-old male presented with two episodes of meningococcal septicaemia, each of which was caused by a different serogroup of Neisseria meningitidis . Examination of the alternative pathway of complement revealed the rare X-linked disorder properdin deficiency (PD) . Meningococcal Infection in complement deficiency states is discussed and the unusual features of this case are highlighted. J Infect Dis, 1995 Jul, 172(1), 296 - 301 Plasma levels of cytokines in primary septic shock in humans: correlation with disease severity; Gardlund B et al.; Thirteen patients (median age, 20 years) with life-threatening primary septic shock (10 meningococcal, 3 pneumococcal infections) were studied prospectively . All had a short history of sepsis (< or = 24 h) and no severe underlying disease . Two (15%) died . The logarithm of the initial plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-1 receptor antagonist (ra), and plasminogen activator inhibitor (PAI)-1 correlated significantly with APACHE II scores (r2 = .67, .57, .68, .81, and .68, respectively) . The plasma levels of endotoxin, TNF-alpha, IL-1 beta, and PAI-1 decreased toward normal levels within the first 24 h of treatment, but IL-6 and IL-1ra levels remained high until clinical recovery . On admission, the molar excess of IL-1ra to IL-1 beta was > 2000-fold in 11 of the 13 patients . Acute plasmapheresis in 11 of the 13 patients significantly increased the plasma clearance of TNF-alpha (P = .02). J Clin Microbiol, 1995 Jul, 33(7), 1784 - 6 Neisseria meningitidis with decreased susceptibility to penicillin in Saskatchewan, Canada; Blondeau JM et al.; Moderately penicillin-resistant Neisseria meningitidis is rare in North America . We report an outbreak of meningococcal disease in Saskatoon, Saskatchewan, Canada, with serogroup C N . meningitidis . The MICs of penicillin ranged from 0.12 to 0.25 micrograms/ml, and all isolates showing decreased susceptibility had identical genomic fingerprints when they were compared by pulsed-field gel electrophoresis . Our data indicate that N . meningitidis that is moderately resistant to penicillin is prevalent in Saskatchewan, Canada. Lancet, 1995 Jul 1, 346(8966), 20 - 3 Control of group C meningococcal disease in Australian aboriginal children by mass rifampicin chemoprophylaxis and vaccination; Pearce MC et al.; An outbreak of 12 cases of meningitis, 11 caused by Neisseria meningitidis serogroup C, occurred at Doomadgee from September, 1990, to April, 1991 . The incidence of meningitis was 17.55/10(3) person-years . Only children aged 1-10 years were affected . In October, 1990, or shortly thereafter, 473/509 children aged between 1 and 15 years inclusive had one dose of Mencevax AC . From the time of vaccination until April, 1991, a further eight cases occurred, six in vaccinated children . Vaccine efficacy in 1-15 year olds was calculated as 77% . Despite this, in April, 1991, the prevalence of antibody to group C polysaccharide in vaccinated children (78%) was not significantly different from that in unvaccinated children and adults . 46 nonresponders were revaccinated, and, in February, 1992, 78% had antibodies to group C polysaccharide . In April, 1991, an estimated 3.0% of the population had group C organisms, carriage being directly related to household crowding . In June, 1991, 2 months after mass prophylaxis with rifampicin, none of these individuals were carriers . In October, 1991, the carriage rate of group C organisms was 0.64% . There have been no further cases caused by the epidemic strain . Although uncrowded housing is a basic need, mass chemoprophylaxis and two doses of vaccine for children should be used in similar outbreaks. Pediatr Infect Dis J, 1995 Jul, 14(7), 557 - 61 Application of new sepsis definitions to evaluate outcome of pediatric patients with severe systemic infections; Saez-Llorens X et al.; No published reports have stratified pediatric patients with systemic infections according to the new sepsis terminology guidelines . In addition little is known about the outcome of sepsis in developing countries . This large 12-year retrospective study evaluated the outcome of 815 infants and children with sepsis managed in a Latin American pediatric intensive care unit . Of these children 171 (21%) had sepsis, 497 (61%) had severe sepsis and 147 (18%) had septic shock . Multiorgan dysfunction was present in 120 (24%) and 77 (52%) patients with severe sepsis and septic shock, respectively . Infection was bacteriologically proved in 212 (26%) cases, with Staphylococcus aureus and Neisseria meningitidis being the most frequent responsible organisms . Three hundred nineteen (39%) patients died . Case-fatality rates were higher in patients with septic shock, multiorgan dysfunction, sepsis caused by Pseudomonas aeruginosa and meningococcemia than in those without these conditions . Although no difference in mortality was detected between culture-proved and culture-negative sepsis, more patients receiving an inappropriate antimicrobial agent died than those treated with an appropriate drug (53% vs . 34%, P = 0.012) . We believe that with the use of the new terminology system a more reliable comparison of data from pediatric sepsis studies and of emerging immunomodulating therapeutic modalities can be achieved. Clin Microbiol Rev, 1995 Jul, 8(3), 376 - 88 Interaction of pathogenic neisseriae with nonphagocytic cells; Nassif X et al.; The ability to interact with nonphagocytic cells is a crucial virulence attribute of the meningococcus and the genococcus . Like most bacterial pathogens, Neisseria meningitidis and Neisseria gonorrhoeae initiate infections by colonizing the mucosal epithelium, which serves as the site of entry . After this step, both bacteria cross the intact mucosal barrier . While N . gonorrhoeae is likely to remain in the subepithelial matrix, where it initiates an intense inflammatory reaction, N . meningitidis enters the bloodstream, and eventually the cerebrospinal fluid to cause meningitis . Both pathogens have evolved very similar mechanisms for interacting with host cells . Surface structures that influence bacterium-host interactions include pili, the meningococcal class 5 outer membrane proteins or the gonococcal opacity proteins, lipooligosaccharide, and the meningococcal capsule . This review examines what is known about the roles these structures play in bacterial adhesion and invasion, with special emphasis, on pilus-mediated adhesion . Finally, the importance of these structures in neisserial pathogenesis is discussed. Microbiology, 1995 Jul, 141 ( Pt 7), 1593 - 600 A linear B-cell epitope on the class 3 outer-membrane protein of Neisseria meningitidis recognized after vaccination with the Norwegian group B outer-membrane vesicle vaccine; Delvig AA et al.; The class 3 outer-membrane protein (OMP) of Neisseria meningitidis is a potential target for bactericidal and opsonic antibodies in humans . Synthetic peptides spanning the class 3 OMP from the vaccine strain 44/76 (B:15:P1.7,16:L3,7) were synthesized on pins and screened with serum obtained from Norwegian adolescents immunized with a meningococcal serogroup B outer-membrane vesicle (OMV) vaccine . A strong IgG response to a single peptide (19FHQNGQVTEVTT30) located within loop 1 (VR1) was stimulated after three doses of OMV vaccine in three vaccinees selected on the basis of their antibody response to class 3 OMP . No clear linear B-cell epitopes were recognized by four different murine serotype 15-specific mAbs . A 23mer peptide (D63b2) containing loop 1 of the class 3 OMP was synthesized, and the IgG responses were measured in pre- and post-vaccination serum from 27 vaccinees . Specific IgG rose significantly in 37% of vaccinees 6 weeks after the second dose and in 74% of the vaccinees 6 weeks after the third dose of the OMV vaccine . Most immune sera reacted distinctly on immunoblots with denatured class 3 OMP, and the immunoblotting reactivity correlated strongly with concentration of the IgG antibodies specific for peptide D63b2 . When added to a post-vaccination serum from one vaccinee, peptide D63b2 competed efficiently with the class 3 OMP for specific antibody binding on immunoblots and in pin ELISA . The results show that the significant part of the humoral response to the meningococcal class 3 OMP elicited by vaccination with the Norwegian OMV vaccine was directed against a single continuous epitope. Mol Microbiol, 1995 Jun, 16(6), 1087 - 97 Functional implications of the expression of PilC proteins in meningococci; Virji M et al.; Multiple forms of PilC were found in Neisseria meningitidis (Nm) strains isolated from the oropharynx, blood or cerebrospinal fluid expressing either Class I or Class II pili . PilC expression was observed less frequently in case as opposed to carrier isolates . Moreover, PilC and pili were not always co-expressed . Several heavily piliated strains had no detectable PilC protein as determined by Western blotting using an antiserum previously used to detect such proteins in adhesive variants (Nassif et al., 1994) . Serogroup B strain MC58 produced large numbers of pili, but expressed barely detectable amounts of PilC . A clonal variant of this strain with increased expression of PilC concurrently exhibited increased adherence to Chang conjunctival epithelial cells and human umbilical vein endothelial cells (Huvecs), but with more rapid binding to the former . No alteration in pilin sequence occurred in this variant, suggesting the involvement of PilC in increased adhesion . A Pil- backswitcher isolated from the hyper-adherent variant was PilC+ but was non-adherent, indicating that any PilC adherence function requires pilus expression . Parental variant (low PilC) produced pili in bundles that were easily detached from the bacterial surface and were frequently associated with Huvec surfaces after bacteria had been sheared off, but pili infrequently replaced bacteria during infection with the PilC-expressing variant . The hyper-adherent variant, which appeared to produce morphologically distinct pilus bundles, was able to withstand considerable shearing force and remained firmly attached to Huvecs . This raises the possibility that the observed hyper-adherence may arise from better anchorage of pili to the bacterial surface in addition to increased adhesion to some host cell surfaces. Microb Pathog, 1995 Jun, 18(6), 423 - 36 The Neisseria meningitidis outer membrane protein P1 produced in Bacillus subtilis and reconstituted into phospholipid vesicles elicits antibodies to native P1 epitopes; Muttilainen S et al.; Class 1 outer membrane protein (P1) of Neisseria meningitidis group B is considered a promising vaccine candidate because P1 subtype-specific antibodies have been shown to be protective in an animal model . We have previously described the production of P1 in the Gram-positive Bacillus subtilis as intracellular inclusion bodies, from which the protein (BacP1) is easily purified (Nurminen et al., Mol . Microbiol., 1992, 2499-2506) . We show here that the purified BacP1 can be reconstituted into phospholipid vesicles with the formation of the native immunodominant surface epitopes . The detergent-solubilized, completely denatured BacP1 was fused with phospholipid-detergent micelles during detergent removal by dialysis or gel filtration to yield protein-lipid vesicles (liposomes) . When mice were immunized with these liposomes, they produced high titers of antibodies reacting in a P1 subtype-specific manner with meningococcal cells indicating the presence of conformation-dependent P1-specific epitopes in the liposomes . The results suggest that a vaccine candidate for meningococcal disease could be developed from the BacP1-liposomes . They furthermore demonstrate the feasibility of refolding a denatured outer membrane protein, which has never been exposed to lipopolysaccharide, into a native-like conformation. J Pediatr, 1995 Jun, 126(6), 937 - 9 Relationship between parental occupation and children's oropharyngeal colonization with Neisseria meningitidis; King WJ et al.; We explored, during an outbreak of meningococcal disease, whether children of parents with workplace exposure to children were at increased risk of oropharyngeal colonization with Neisseria meningitidis . In comparison with children of parents without workplace exposure to children, the risk of colonization was not increased (odds ratio = 1.62; 95% confidence interval, 0.56 to 4.72) . Therefore a parent's occupation does not appear to increase the risk of their children's colonization with N . meningitidis. J Infect Dis, 1995 Jun, 171(6), 1481 - 90 Antibodies to polysialic acid and its N-propyl derivative: binding properties and interaction with human embryonal brain glycopeptides; Hayrinen J et al.; There is no efficient vaccine against group B meningococcal meningitis because of tolerance induced by host tissue polysialic acid cross-reacting with the capsular polysaccharide . The specificities of polysialic acid-antibody interactions were studied using a ligand binding assay . Antibodies 735, 20-1, 2-1B, 2-2B, 5E1, and t5E1 and antibodies against N-propionylated group B meningococcal polysaccharide-tetanus toxoid conjugate (NP-4, 106-6) bound polysialylated human embryonal brain glycopeptides but not control glycopeptides or disialosyllactose, whereas antibodies 109-3 and I-627 were more specific for the N-propionylated polysaccharide . Antiganglioside antibodies (KM538, KM641) did not cross-react with polysialic acid . Human class-switched antibodies 5E1 (IgM) and t5E1 (IgG) reacted identically with all compounds tested and no temperature-dependent differences were observed . All anti-polysialosyl antibodies required a polysaccharide chain of 8-10 residues for binding independent of the immunizing antigen, animal species, or immunoglobulin class . The results suggest careful evaluation of polysialic acid cross-reactivity in vaccine development. Infect Immun, 1995 Jun, 63(6), 2109 - 12 High levels of interleukin 10 in serum are associated with fatality in meningococcal disease; Lehmann AK et al.; Interleukin 10 (IL-10) suppresses the production of proinflammatory cytokines in vitro and in murine models of endotoxemia and has been suggested as a candidate for treatment of bacterial septicemia . To investigate the role of IL-10 in meningococcal disease, a sandwich IL-10 enzyme-amplified sensitivity immunoassay was used to quantitate IL-10 in serum and cerebrospinal fluid samples from 41 patients with meningococcal bacteremia or meningitis with or without septic shock . High levels of IL-10 were demonstrated in sera from patients with meningococcal septic shock (mean, 21,221 pg/ml; range, 25 to 64,500 pg/ml) . All cases involving fatalities had IL-10 levels in serum of > or = 1,000 pg/ml (mean, 23,058 pg/ml; range, 1,000 to 64,500 pg/ml) . Patients with meningococcal meningitis without septic shock had comparably low concentrations of IL-10 in serum (mean, 119 pg/ml; range, 0 to 1,050 pg/ml) but exhibited compartmentalized release of IL-10 in cerebrospinal fluid . Concentrations of IL-10 in serum were positively correlated with the previously reported concentrations of tumor necrosis factor alpha, IL-6, and IL-8 in serum in the same patients . We conclude that IL-10 is extensively activated along with the proinflammatory cytokines during the initial phase of meningococcal septic shock and that IL-10 is associated with fatality in meningococcal disease. Am J Public Health, 1995 Jun, 85(6), 843 - 5 Should college students be vaccinated against meningococcal disease? A cost-benefit analysis; Jackson LA et al.; Outbreaks and sporadic cases of meningococcal disease among college students have prompted consideration of a policy of routine vaccination for this group . Purchase and administration of the vaccine for routine vaccination would cost $56 million per year . Savings in medical care and indirect costs would not equal this amount unless the annual rate of disease among students is at least 6.5/100,000 . The actual rate among students is unknown; however, surveillance data suggest it could not be more than 1.3/100,000 . At rates near this estimate, the net cost of the program would be approximately $45 million annually . More cost-effective prevention strategies might be yielded by further studies to identify students at substantial risk of meningococcal disease, or by the development of a conjugate serogroup C vaccine that could be administered during infancy. Eur J Pediatr, 1995 Jun, 154(6), 472 - 4 The changing presentations of meningococcal disease; Riordan FA et al.; Meningococcal disease (MCD) can present as meningitis, meningitis plus septicaemia or septicaemia alone . This 17-year retrospective study sought to determine if the proportion of cases presenting as septicaemia alone was increasing . Four hundred and forty-nine children with MCD were admitted between 1977 and 1993, 50 children died (11%) . The proportion of cases with septicaemia alone increased from 7% in 1977-1985 to 36% in 1990-1993 (P < 0.0005) . Mortality was highest in children with septicaemia alone (19%) . Despite the increase in septicaemia, overall mortality did not alter over the 17 years . CONCLUSION: MCD should not be thought of as "meningitis", since 33% of cases now present as septicaemia alone . Nearly one in five children with septicaemia alone die . Information and publicity about MCD should focus on septicaemia, characterised by a petechial rash, as the life-threatening presentation. Acta Trop, 1995 Jun, 59(3), 211 - 22 The 1990 meningococcal meningitis epidemic of Sarh (Chad): how useful was an earlier mass vaccination? Lengeler C, Kessler W, Daugla D. A large outbreak of meningococcal meningitis (Serogroup A) occurred in southern Chad in 1990 . We describe the epidemic in the town of Sarh, where a mass vaccination against meningococcal meningitis had taken place two years before, in 1988 (estimated coverage: 66%) . Early warning that an epidemic was imminent was given at the end of February, following more than 15 recorded cases per 100,000 population on 3 consecutive weeks . This threshold proved to be adequate to predict the outbreak . A total of 721 cases were recorded at Sarh hospital and at a nearby health centre . Direct agglutination tests confirmed that Neisseria meningitis serogroup A was the only causative agent . The overall incidence rate in this population of 80,000 was 0.9% . The highest weekly incidence rate was 186 cases per 100,000 population . The mean age of the patients was 12.6 years and age-specific incidence rates ranged from 0.23% to 1.42% . The male/female sex ratio was 1.36 . Overall, the mortality among hospitalized patients was 7.9% . Mortality increased during the epidemic . The major risk factor for dying was the delay until reaching hospital . Only 4 out of 29 interviewed parents said that their child had been vaccinated two years before . Among adult patients this proportion was 12/38 (32%) . Because of the small numbers and because of the impossibility to check the vaccination records it was not possible to assess precisely the impact of earlier mass vaccination . However, the previous mass vaccination did not prevent this major epidemic and its impact is likely to have been unimportant. Vaccine, 1995 Jun, 13(9), 821 - 9 Efficacy, safety, and immunogenicity of a meningococcal group B (15:P1.3) outer membrane protein vaccine in Iquique, Chile . Chilean National Committee for Meningococcal Disease; Boslego J et al.; A meningococcal group B (15:P1.3) outer membrane protein vaccine was tested for efficacy in a randomized, double-blind controlled study in Iquique, Chile . A total of 40 811 volunteers, ages 1-21 years, enrolled in the study . Volunteers received two doses of vaccine six weeks apart by jet injector . Both the experimental vaccine and the control vaccine (Menomune, A, C, Y and W135 meningococcal polysaccharide vaccine) were well tolerated with minor side-effects . Active surveillance for suspected cases of meningococcal disease was conducted for 20 months in Iquique . Eighteen cases of group B meningococcal disease were confirmed during the 20 months . Efficacy was estimated to be 51% (p = 0.11) for all ages combined . In children aged 1-4 no protection was evident, but in volunteers aged 5-21 vaccine efficacy was 70% (p = 0.045) . The IgG antibody response by ELISA was characterized by a large booster effect after the second dose, followed by a substantial drop in antibody levels by 6 months . The youngest children had the highest responses . The bactericidal antibody response, on the other hand, was characterized by the lack of a significant booster response, higher responses in the older children, and an increase in the geometric mean titer in the later months of the study in the older children. Gene, 1995 May 26, 158(1), 145 - 6 Diversity of the transferrin-binding protein Tbp2 of Neisseria meningitidis; Mazarin V et al.; In order to investigate the genetic basis for the observed polymorphism amongst meningococcal transferrin-binding proteins, Tbp2, the corresponding genes of different Neisseria meningitidis strains were cloned and sequenced . Comparison of the deduced amino acid (aa) sequences indicated that the Tbp2 were 76.6 to 81.2% homologous . Several stretches of aa have been found repeated both in the N- and C-terminal halves of the molecule. J Med Microbiol, 1995 May, 42(5), 353 - 61 Experimental infection of human nasal mucosal explants with Neisseria meningitidis; Read RC et al.; The interaction of Neisseria meningitidis with rhinopharyngeal epithelium was studied by experimental infection of explants of human nasal turbinate mucosa with two wild strains: a fully capsulate case isolate, and an epidemiologically related non-capsulate nasopharyngeal isolate . After incubation for 4 h, epithelial cells of infected explants changed conformation from tall columnar morphology towards cuboidal, and there was increased discharge of mucus globules from goblet cells . By 24 h there was significant damage to infected epithelia, including projection of cells out of the surface, cytoplasmic blebbing and mitochondrial abnormalities . Meningococci were associated with surface non-ciliated cells by 4 h after infection . By 24 h after infection they were associated extensively with all cell types exhibiting damage . There was little association with secreted mucus . In areas of cell damage, penetration between surface cells was observed . Endocytosis into non-ciliated cells was observed in only a minority of explants studied and only in those infected for 24 h . From this intracellular site there was apparent migration to adjacent cells and to intercellular locations . No organisms were observed within or beneath basement membrane collagen in any explants but internalisation into mononuclear phagocytes was observed occasionally. FEMS Microbiol Lett, 1995 May 1, 128(2), 145 - 50 Sequence variation in class 1 outer membrane protein in Neisseria meningitidis isolated from patients with meningococcal infection and close household contacts; Brooks JL et al.; The meningococcal porA gene encodes the class 1 outer membrane protein which contains the VR1 and VR2 regions responsible for sero-subtype specificity . However, sequence variations may occur within these regions which are not recognised by the currently available subtype antibodies . Since this "silent" microheterogeneity represents a potential hidden source of information, in the current study we have used porA gene sequence analysis to study strains isolated from cases of meningococcal infection and close household contacts . With each of the three subtypes studied, the index cases could be differentiated from each other by sequence variations within at least one of the VR1, VR2 and SV1 regions . In addition, although isolates from close household contacts showed a high degree of homology significant differences could be detected within some family groups . These data demonstrate that it is possible to use sequence information to differentiate between potential sources of infection which appear identical using conventional serological methods. J Bacteriol, 1995 May, 177(9), 2475 - 80 Variable expression of class 1 outer membrane protein in Neisseria meningitidis is caused by variation in the spacing between the -10 and -35 regions of the promoter; van der Ende A et al.; The class 1 outer membrane protein encoded by the porA gene of Neisseria meningitidis is a candidate for a vaccine against meningococcal infection . The expression of class 1 outer membrane protein displays phase variation between three expression levels . Northern (RNA) blot and primer extension analysis revealed that this phase variation is regulated at the transcriptional level . The start site for transcription is located 59 bp upstream of the translational initiation codon . Sequence analysis of the promoter region of the porA gene of a variant without class 1 protein expression revealed nine contiguous guanidine residues between the -10 and -35 domains . Comparison of promoter sequences of different phase variants indicated that the length of the polyguanidine stretch correlated with the expression level of the class 1 outer membrane protein; the presence of 11, 10, or 9 contiguous guanidine residues results in high levels, medium levels, or no expression of class 1 mRNA, respectively . These results suggest that the variable porA expression levels seen in different isolates are modulated by guanidine residue insertion and/or deletion due to slipped-strand mispairing on the polyguanidine stretch within the intervening sequence of the -35 and -10 regions of the promoter . The phase variation of class 1 outer membrane protein may provide a molecular mechanism to evade the host immune defense . Therefore, the protective efficacy of a vaccine based on class 1 outer membrane protein may be questioned. Infect Immun, 1995 May, 63(5), 1624 - 30 Cloning and characterization of the meningococcal polyphosphate kinase gene: production of polyphosphate synthesis mutants; Tinsley CR et al.; The pathogenic Neisseria species accumulate polyphosphate to levels between 10 and 20% of their total phosphate content . However, the significance of this compound for the growth and pathogenicity of these species is not understood . A previous report (C.R . Tinsley, B.N . Manjula, and E.C . Gotschlich, Infect . Immun . 61:3703-3710, 1993) describes the purification of polyphosphate kinase, the enzyme responsible for synthesis of polyphosphate, from Neisseria meningitidis BNCV . By use of probes based on the amino acid sequence of the purified enzyme, the structural gene ppk has been cloned and sequenced . The coding sequence is 2,055 bp long and codes for a protein of 77.2 kDa . The open reading frame of the cloned gene was interrupted by the insertion of a kanamycin resistance cassette, and ppk mutants were obtained in both Neisseria gonorrhoeae and N . meningitidis by transformation with the recombinant plasmid . Amounts of polyphosphate in the ppk mutants were reduced to between 2 and 10% of wild-type levels . The mutants grew less vigorously than wild-type organisms in vitro and showed a striking increase in sensitivity to killing by human serum. Clin Diagn Lab Immunol, 1995 May, 2(3), 314 - 21 Emergence of a new virulent clone within the electrophoretic type 5 complex of serogroup B meningococci in Norway; Wedege E et al.; An increase in B:15:P1.12 meningococci among isolates from patients with Neisseria meningitidis infection in Norway in recent years led to further characterization of such strains . Between 1987 and 1992, B:15:P1.12 strains constituted 9.8% (24 strains) of B:15 isolates . The B:15:P1.12 strains belonged to the electrophoretic type 5 (ET-5) complex, but 17 (71%) strains were a new clone (ET-5c) not found elsewhere in the world . All but one strain of ET-5c were responsible for a localized outbreak of systemic meningococcal disease in western Norway . A novel monoclonal antibody (202,G-12), developed against the unknown variable region 2 on the class 1 protein of one of these strains, bound to 19 of the 15:P1.12 strains, 4 strains bound the subtype P1.13 reference monoclonal antibody MN24H10.75, and the remaining strain showed no reaction . Sequencing of porA genes demonstrated a series of nine threonine residues in the deduced variable region 2 of the latter strain, while four and five threonine residues were found in the corresponding regions of strains reacting with the monoclonal antibodies 202,G-12 and MN24H10.75, respectively . Epitope mapping with synthetic peptides showed that 202,G-12 bound to a sequence of 11 amino acids which included the four threonine residues specific for subtype P1.13a . Immunoglobulin G antibodies against the P1.7,16 subtype protein, induced in volunteers after vaccination with the Norwegian meningococcal vaccine, did not cross-react on immunoblots with the subtype protein of clone ET-5c . Thus, postvaccination class 1 protein antibodies, assumed to be protective, may not be effective against infection with the new clone. Trends Microbiol, 1995 May, 3(5), 186 - 92 Epidemic spread and antigenic variability of Neisseria meningitidis; Achtman M; Genetic variation of cell-surface antigens of serogroup A meningococci arises from horizontal genetic exchange . Most clonal variants are lost by clonal reduction during epidemic and pandemic spread, but in exceptional cases, genetic variants are rapidly fixed in the bacterial population by clonal replacement. Arch Dis Child, 1995 May, 72(5), 441 - 2 Hearing assessment after meningitis and meningococcal disease; Riordan A et al.; A method to increase audiology referral after meningitis or meningococcal disease was audited in 89 children . A standardised proforma increased referrals from 78% to 96% over a two year period . However, only 73% of children had a hearing test . The major reason for hearing not being tested changed from non-referral to non-attendance. Public Health Rep, 1995 May-Jun, 110(3), 343 - 9 Epidemiologic characteristics of an outbreak of serogroup C meningococcal disease and the public health response; Houck P et al.; An outbreak of serogroup C meningococcal disease occurred in six counties in the State of Washington from January 1989 through mid-1991 . This report describes epidemiologic data collected from hospitals and health departments, the results of multilocus enzyme electrophoresis of isolates, and the vaccination of high-risk populations in one county . A total of 45 confirmed or probable cases (10 per 100,000 population) occurred . Infants younger than age 1, Hispanics and American Indians, and low-income populations had high attack rates . Nine (20 percent) patients died . The predominant enzyme type, ET-22, had not been detected previously in Washington . More than 22,000 persons were vaccinated in one of the counties . Major challenges to health care personnel included deciding when and where to employ vaccination, obtaining sufficient vaccine, and responding to public anxiety. J Antimicrob Chemother, 1995 May, 35(5), 687 - 90 Antimicrobial susceptibility of penicillin-sensitive and penicillin-resistant meningococci; Abadi FJ et al.; Ceftriaxone showed high in-vitro activity against 119 penicillin-sensitive, penicillin-resistant and rifampicin-resistant UK isolates of meningococci . Unlike ciprofloxacin and minocycline, ceftriaxone is suitable for use in young children or in pregnancy and should be considered for therapy or prophylaxis in an outbreak of meningococcal disease . The E test gave results comparable to those given by broth microdilution method in the determination of meningococcal susceptibility to antimicrobials . It is convenient for use in small laboratories and can be used to determine antimicrobial subgroups of meningococci. Microb Pathog, 1995 May, 18(5), 365 - 71 Heterologous production of the P1 porin of Neisseria meningitidis in bacillus subtilis: the effect of an N-terminal extension on the presentation of native-like epitopes; Muttilainen S et al.; The major outer membrane protein P1 (class 1) of Neisseria meningitidis has been produced as inclusion bodies in Bacillus subtilis with the aim to develop a vaccine based on it . The protein produced in high yield in B . subtilis contained an N-terminal extension of 11 amino acid residues which was found to be necessary for expression in the production system . In the present study we asked whether or not the removal of this extension would effect the conformation of this protein in liposomes as judged by its immunogenic properties . A methionine was engineered in front of the mature P1 protein to provide a chemical cleavage site for CNBr to remove the extension . The CNBr-cleaved protein, complexed with phospholipids, elicited high titers of antibodies binding to the meningococcal cells similarly to the noncleaved protein . This suggests that the BacP1 protein can serve as an effective vaccine component irrespective of the presence, or absence, of this N-terminal extension. Commun Dis Rep CDR Rev, 1995 Apr 28, 5(5), R61 - 8 The infection hazards of human cadavers; Healing TD et al.; Cadavers may pose infection hazards to people who handle them . None of the organisms that caused mass death in the past--for example, plague, cholera, typhoid, tuberculosis, anthrax, smallpox--is likely to survive long in buried human remains . Items such as mould spores or lead dust are much greater risks to those involved in exhumations . Infectious conditions and pathogens in the recently deceased that present particular risks include tuberculosis, group A streptococcal infection, gastrointestinal organisms, the agents that cause transmissible spongiform encephalopathies (such as Creutzfeldt-Jakob disease), hepatitis B and C viruses, HIV, and possibly meningitis and septicaemia (especially meningococcal) . The use of appropriate protective clothing and the observance of Control of Substances Hazardous to Health regulations, will protect all who handle cadavers against infectious hazards. Proc Natl Acad Sci U S A, 1995 Apr 25, 92(9), 4021 - 5 Peptide mimicry of the meningococcal group C capsular polysaccharide; Westerink MA et al.; Sequence analysis of the variable regions of the heavy and light chains of the anti-idiotypic antibody 6F9, which mimics the meningococcal group C capsular polysaccharide (MCP), was performed . The immunogenic site on 6F9 responsible for inducing an anti-MCP antibody response was determined by means of sequence and computer model analysis of these data . Complementarity-determining region 3 (CDR3) was found to be unique in that the sequence tract YRY was exposed on the surface . A synthetic peptide spanning the CDR3 domain was synthesized and complexed to proteosomes (meningococcal group B outer membrane protein) . Immunizations of BALB/c mice with the peptide-proteosome complex resulted in a significant anti-MCP antibody response . Immunized mice were protected against infection with a lethal dose of Neisseria meningitidis serogroup C. J Immunol Methods, 1995 Apr 12, 181(1), 125 - 35 A monoclonal antibody against Meningococcus group B polysaccharides used to immunocapture and quantify polysialylated NCAM in tissues and biological fluids; Dubois C et al.; Polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) are transiently expressed in many tissues during development and in discrete areas of the adult central nervous system . In pathological situations, they are expressed by poorly differentiated tumor cells of neuroectodermal origin and by regenerating muscle . An ELISA is introduced here to estimate the relative concentrations of PSA-NCAM expressed by tissues or released into biological fluids . In this double-sandwich assay, an anti-PSA antibody (anti-MenB) was adsorbed onto plastic plates and permitted the immunocapture of PSA-bearing molecules . It is demonstrated that these molecules are major NCAM . The second antibody was directed against an amino acid sequence shared by NCAM isoforms in several species . The standard curves were established using Nonidet P40 extracts of human or mouse embryonic brain known to be rich in PSA-NCAM . The sensitivity of the assay allows for quantitation of PSA-NCAM in muscle during regeneration and in small samples of cerebrospinal fluid from patients with medulloblastoma metastasis. Lancet, 1995 Apr 8, 345(8954), 886 - 9 Mannose binding protein gene mutations associated with unusual and severe infections in adults; Summerfield JA et al.; A defect in opsonisation can cause a common immunodeficiency . A mutation in mannose binding protein (MBP) caused by point mutations in the MBP gene will lead to such a defect . This type of syndrome can cause recurrent infections in infants between 6 and 18 months of age but is not generally believed to predispose to adult infections . We looked at 4 patients with severe and unusual infections in whom MBP gene mutations were the only identified cause of immunodeficiency and one patient with combined MBP and IgA deficiency . We analysed the MBP genotypes of all the patients in whom we suspected an immunodeficiency because of their clinical history . Infections seen were recurrent skin abscesses, chronic cryptosporidial diarrhoea, meningococcal meningitis with recurrent herpes simplex, and fatal klebsiella lobar pneumonia . Both sexes were affected and ages ranged from 15 to 56 years . Two patients were homozygous for codon 54 mutations, one patient had codon 52 and codon 54 mutations and was phenotypically homozygous, and two patients were heterozygous for codon 54 mutations . Individuals homozygous for MBP mutations are unusual in the general population (approximate frequency 0.3%) . The occurrence of three homozygotes for MBP mutations among these five infected patients suggests that MBP deficiency may confer a life-long risk of infection. Infect Immun, 1995 Apr, 63(4), 1603 - 7 Isolation and identification of a glutathione peroxidase homolog gene, gpxA, present in Neisseria meningitidis but absent in Neisseria gonorrhoeae; Moore TD et al.; Antioxidant enzymes are thought to be important for the survival of pathogenic Neisseria species . We isolated a glutathione peroxidase-related gene (gpxA) from Neisseria meningitidis FAM20 . The N . meningitidis glutathione peroxidase homolog was 49 to 57% identical to seven other glutathione peroxidase family members over a 49-amino-acid region which is conserved among various species . The gpxA sequence was pres