Meningococcus

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 present in all 7 meningococcal strains tested but absent in 10 gonococcal strains and 6 nonpathogenic neisserial strains as determined by Southern hybridization . The homology of gpxA to mammalian glutathione peroxidases and the presence of this gene specifically in the meningococcus suggest that it is important in the cellular metabolism or defense processes particular to this pathogen.

Infect Immun, 1995 Apr, 63(4), 1484 - 90
Analysis of Neisseria meningitidis class 3 outer membrane protein gene variable regions and type identification using genetic techniques; Bash MC et al.; The class 3 porin proteins of Neisseria meningitidis stimulate bactericidal antibodies and express serotype-specific antigenic epitopes . Sequence analysis of porB genes for the class 3 proteins revealed regions of variability that map to surface-exposed loops . To evaluate the relationship between serotype and variable-region (VR) genotype, sequences from the 11 class 3-expressing serotype strains and 3 additional serotype 4 strains were analyzed by molecular techniques . Multiple-sequence alignment revealed a limited number of unique sequences at each of four VRs (VR1 to VR4), ranging from four unique sequences at VR1 to seven sequence patterns at VR2 and VR4 . Serotype-specific VR sequences were found in each of the four VRs, suggesting that each VR has immunologic importance . Five serotypes had at least one VR sequence that was unique . Three serotypes which had sequences in common with other serotypes at each VR were distinguished by examining multiple VRs . Serotype 3 was identical to serotype 19 at each VR, and serotype 8 was identical to serotype 18 at each VR . Serotypes 4 and 21 were identical at VR1 and significantly different at VR3 and VR4 . A subpopulation of serotype 4 strains with a unique VR2 sequence was identified . The serotypes which were grouped with closely related or identical sequences at one VR were grouped with different serotypes at other VRs consistent with the pattern of genetic mosaicism described for the porA (class 1 protein) gene . Hybridization assays demonstrated the ability to identify VR genotypes and distinguish serotypes using biotin-labelled oligonucleotide probes . This information may be useful in strain selection for vaccine development, in epidemiologic studies to determine the prevalence of the individual VR genotype (especially among nonserotypeable strains) and, combined with PCR, in the identification of culture-negative suspected meningococcal cases.

Bol Oficina Sanit Panam, 1995 Apr, 118(4), 285 - 94
{Humoral immune response to the proteins of an antimeningococcal BC vaccine in a trial carried out in Antioquia, Colombia}; Echeverry Uribe ML et al.; This study evaluated the humoral response to protein components of the Cuban-produced vaccine against serogroups B and C meningococcus, VA-MENGOC-BC, in adults and children 1 to 5 years old . The trial was conducted in an area of the Department of Antioquia, Colombia, in which an elevated incidence of meningococcal disease had been recorded . The serum anti-vaccine-protein response was studied before (T0) and after (T1) vaccination by means of enzyme-linked immunosorbent assay (ELISA), and lytic capacity was evaluated through the bactericidal antibodies test (BAT) . The ELISA was performed before and after vaccination on the sera of 407 adults and 213 children . Lytic capacity against Cuban meningococcal strain B:4:P1.15 was studied with BAT in paired sera from 90 adults and 114 children . The two techniques showed a statistically significant response (P < 0.01) to the vaccine, in both adults and children . Of the total number of subjects tested with ELISA, 81% showed an immune response to the vaccine (T1/T0 > or = 2) (95% confidence interval, CI95%: 78% to 84%); among children, immune response was 91% (CI95%: 87% to 94%) . All the children 1 year of age (n = 7) responded . Seroconversion (T1/T0 > or = 4), as shown by ELISA, was 80% among adults (CI95%: 73% to 86%) and 90% among children (CI95%: 83% to 100%) . BAT demonstrated seroconversion in 85% (CI95%: 78% to 92%) of subjects who had been seronegative before vaccination, 85% of the adults (CI95%: 76% to 95%) and 84% of the children (CI95%: 72% to 96%) . Seroconversion among children 3 and 4 years of age was 80% . The group of sera from children 1, 2, and 5 years old available for study with BAT was too small for meaningful statistical analysis; all of them seroconverted . In 20 sera chosen randomly for study of their bactericidal activity against all the strains isolated from patients in Colombia (B:4:P1.15, B:8:P1.nt, and two strains of serogroup C), seroconversion was found in all 20 cases . These results give reason to think that vaccination in this group produced an effective immune response, as measured serologically, and this belief is corroborated in practice by the lack of any cases of meningococcal disease through September 1994 among the people vaccinated.

J Infect Dis, 1995 Apr, 171(4), 948 - 53
Effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) on cerebrospinal fluid inflammation induced by endotoxin; Kartalija M et al.; Endotoxin triggers the subarachnoid inflammation of gram-negative meningitis . This study examined the ability of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) to block endotoxin-induced meningitis in rabbits . Intracisternal (ic) injection of 10-20 ng of meningococcal endotoxin induced high cerebrospinal fluid (CSF) concentrations of tumor necrosis factor (TNF) and CSF pleocytosis and increased CSF lactate concentrations . ic administration of rBPI23 significantly reduced meningococcal endotoxin-induced TNF release into CSF (P < .005), lactate concentrations (P < .001), and CSF white blood cell counts (P < .01) . No such effect was observed in animals receiving intravenous rBPI23 . Concentrations of rBPI23 in CSF were high after ic administration but low or undetectable after systemic administration . Thus, high concentrations of rBPI23 can effectively neutralize meningococcal endotoxin in CSF, but low CSF concentrations after systemic administration currently limit its potential usefulness as adjunctive drug treatment in gram-negative meningitis.

J Infect Dis, 1995 Apr, 171(4), 1057 - 60
Release of tumor necrosis factor: an innate host characteristic that may contribute to the outcome of meningococcal disease; Westendorp RG et al.; Tumor necrosis factor (TNF) plays a pivotal role in meningococcal disease . The TNF response to endotoxin, however, differs between individuals and can be determined in whole blood samples ex vivo . The release of TNF in whole blood samples from 50 survivors of meningococcal disease 6-58 months after hospital discharge was studied . The TNF response was higher in patients who had experienced a moderately severe disease course compared with patients with a mild course . The TNF response was low again in the survivors of fulminant disease, who on original hospital admission presented with risk factors exposing them to a high chance of mortality (50% overall) . On admission, the patients who did not survive had initial TNF levels three times higher than those in survivors with a clinical disease presentation of similar severity . Overall interpretation of these findings is that the innate TNF response may contribute to the outcome of meningococcal disease.

J Pediatr, 1995 Apr, 126(4), 646 - 52
Treatment of purpura fulminans in meningococcemia with protein C concentrate; Rivard GE et al.; OBJECTIVE: To evaluate the clinical and laboratory effects of protein C concentrate as an adjunct to conventional therapy in the treatment of meningococcemia with purpura fulminans . DESIGN: Case series (pilot study) . SETTING: Intensive care unit in a tertiary care pediatric hospital . PATIENTS: Four children (aged 3 months to 15 years) requiring intensive treatment for meningococcemia with shock, disseminated intravascular coagulation, and purpura fulminans . INTERVENTION: Intravenous administration of a protein C concentrate (100 IU/kg every 6 hours) . MAIN OUTCOME MEASURES: Plasma protein C amidolytic activity, fibrinogen, and D-dimers; evolution of skin and limb lesions . RESULTS: Treatment with protein C concentrate led to a rise in plasma protein C activity levels to within normal limits in all patients, associated with an increase in plasma fibrinogen and a bimodal decrease in D-dimers . No adverse effects were noted . All patients had reversal of organ dysfunction despite the severity of the initial illness . Two patients recovered completely with no sequelae; two required amputations . CONCLUSIONS: These encouraging clinical and laboratory results and the absence of side effects warrant the initiation of a double-blind, randomized controlled multicenter trial to determine the role of protein C replacement in the treatment of meningococcemia-associated purpura fulminans.

Clin Exp Immunol, 1995 Apr, 100(1), 32 - 9
Vaccination of patients deficient in a late complement component with tetravalent meningococcal capsular polysaccharide vaccine; Platonov AE et al.; Eighteen patients with late complement component deficiency (LCCD) were immunized with meningococcal capsular polysaccharide vaccine . The LCCD patients had experienced one-to-five meningococcal infections before vaccination, but their immunological and clinical status was normal at the time of immunization . Serum samples from vaccinated complement-sufficient relatives of the LCCD patients and healthy Russian male adults were used as controls . Total and immunoglobulin-specific concentrations of antibodies to group A, C, W135, and Y capsular polysaccharides were determined by enzyme immunoassay in serum samples taken before and 1-108 weeks after immunization . The individual preimmunization and post-immunization antibody concentrations varied greatly . The median antibody concentrations of the LCCD patients increased significantly after vaccination, and were not significantly different from those of the control groups . The antibody concentrations remained elevated for at least 1 year after vaccination . The post-immunization antibody concentrations correlated with the number of meningococcal infections within 10 years before vaccination . In spite of the vaccination two LCCD patients experienced a meningococcal disease 9 and 12 months, respectively, after vaccination.

Vaccine, 1995 Apr, 13(5), 463 - 70
Immunogenicity of meningococcal B polysaccharide conjugated to tetanus toxoid or CRM197 via adipic acid dihydrazide; Bartoloni A et al.; Vaccine development against Group B Neisseria meningitidis is complicated by the nature of the capsular polysaccharide, which is alpha 2-8-linked poly-sialic acid, identical in structure to the poly-sialic acid found in many mammalian tissues during development . To test the feasibility of a vaccine based on this polysaccharide, we synthesized several conjugates of meningococcal B polysaccharide linked to a carrier protein (tetanus toxoid or diphtheria CRM197), via an adipic acid dihydrazide (ADH) spacer . All conjugates induced a strong immune response . However, most of the antibodies were not directed against the Meningococcus B polysaccharide and could not be inhibited by the purified polysaccharide alone . Further investigations showed that the antibodies recognized an epitope composed by the junction between the spacer and the polysaccharide and protein, that is not present in the native polysaccharide and is generated during the coupling reaction . This epitope becomes immunodominant with respect to the poorly immunogenic polysaccharide . While the majority of the immune response is directed against the above epitope, the conjugates induced also an immune response against the Meningococcus B polysaccharide . The anti-Meningococcus B antibodies elicited are of the IgM and IgG class and are inhibitable by the polysaccharide . Moreover, they are bactericidal, thus suggesting that they would induce protection against disease.

Microb Pathog, 1995 Apr, 18(4), 289 - 96
Use of antibiotics to select auxotrophic mutants of Neisseria meningitidis; Erwin AL et al.; Antibiotic selection of auxotrophs has been a powerful tool in the elucidation of bacterial metabolic pathways, but it has been difficult to adapt this method to Neisseria spp . We describe a procedure by which a population of mutagenized N . meningitidis is enriched for mutants with specific growth phenotypes . These experiments used a simple defined medium (modified from that described in J Bacteriol 1962; 83: 470-4) in which meningococci grow well on a variety of carbon sources . Nitrosoguanidine-treated meningococci were incubated with an antibiotic (cefotaxime, streptomycin or nalidixic acid) in a defined medium that was nonpermissive for the desired phenotype . The survivors were grown for several generations in a permissive defined medium to reduce the proportion of mutants with phenotypes other than that desired, then subjected to a second antibiotic treatment in nonpermissive medium . Survivors of the second antibiotic treatment were plated, and colonies were screened to identify auxotrophs . This procedure has allowed the isolation of meningococcal mutants with amino acid or vitamin requirements or with altered utilization of carbon sources.

J Infect Dis, 1995 Mar, 171(3), 728 - 31
Eradication of nasopharyngeal carriage of Neisseria meningitidis in children and adults in rural Africa: a comparison of ciprofloxacin and rifampicin; Cuevas LE et al.; A randomized comparative study of rifampicin and ciprofloxacin for eradicating nasopharyngeal carriage of meningococci was undertaken in Malawi . Of 1878 contacts of persons with meningococcal meningitis, 1875 were evaluatable for safety and efficacy of the drugs . Rifampicin was given to 836 contacts, ciprofloxacin to 711, and ceftriaxone to 328 (children < 2 years old or pregnant or lactating women) . One and 2 weeks after therapy, side effects in those given rifampicin and ciprofloxacin were not significantly different . In the ciprofloxacin group, with 470 subjects < 18 years old, only one event (mild abdominal pain) occurred that was related to the drug . Nasopharyngeal carriage was detected in 88 (10.5%) of those given rifampicin, 79 (11.1%) given ciprofloxacin, and 41 (12.5%) given ceftriaxone . Eradication rates after 1 and 2 weeks of treatment, respectively, were 96.5% and 97.7% for rifampicin, 88.6% and 91.1% for ciprofloxacin, and 95.1% and 97.6% for ceftriaxone . Ciprofloxacin provides a safe and effective alternative to rifampicin for eradication of meningococcal carriage in children 2-18 years old.

J Infect Dis, 1995 Mar, 171(3), 632 - 8
A trial of a group A plus group C meningococcal polysaccharide-protein conjugate vaccine in African infants; Twumasi PA Jr et al.; The safety and immunogenicity of a group A plus group C meningococcal polysaccharide-CRM197 conjugate vaccine was evaluated in 304 8- to 10-week-old Gambian infants . Infants were immunized with one, two, or three doses of conjugate vaccine or with two doses of a meningococcal A plus C polysaccharide vaccine . The conjugate vaccine produced few systemic side effects, and local reactions were similar to those produced by the polysaccharide vaccine . Postvaccination group A meningococcal polysaccharide antibody levels, measured by ELISA, increased progressively after one, two, or three doses of conjugate vaccine . However, one dose of conjugate vaccine given at the age of 6 months induced a higher group C meningococcal antibody response than did two doses of conjugate vaccine given at 2 and 6 months . Two doses of conjugate vaccine induced higher levels of antibody than did two doses of polysaccharide vaccine . Thus, this new meningococcal conjugate vaccine proved to be safe and immunogenic.

Infect Immun, 1995 Mar, 63(3), 884 - 90
Evaluation of transferrin-binding protein 2 within the transferrin-binding protein complex as a potential antigen for future meningococcal vaccines; Lissolo L et al.; Because the meningococcal transferrin receptor was shown to elicit bactericidal and protective antibodies in laboratory animals, we undertook a study of the protective role of each of the polypeptides within the Tbp1-Tbp2 complex . We developed a procedure to purify from Neisseria meningitidis B16B6 the two proteins in milligram amounts and raised specific antisera in rabbits and mice . Only antisera specific for Tbp2 displayed bactericidal activity against the parent strain . Mice immunized with purified Tbp2 survived a lethal challenge to a similar degree as animals immunized with the Tbp1-Tbp2 complex, demonstrating that Tbp2 played an important role in the protective activity observed with the complex . Both Tbp1- and Tbp2-specific antisera inhibited transferrin binding to the purified receptor in a solid-phase binding assay, suggesting that the antibodies were able to interact with the Tbp1 molecule only when it was removed from its membrane environment . Finally, Tbp2-specific immunoglobulins were able to lower the growth rate of the meningococci when human transferrin was their sole iron source . Therefore, in all four different systems tested, Tbp2 or antibodies specific for Tbp2 displayed biological characteristics close to those of the Tbp1-Tbp2 complex . This suggests that Tbp2 plays an important role in the protective activity of the complex, eliciting antibodies that are not only bactericidal but also inhibitory for meningococcal growth.

Vaccine, 1995 Mar, 13(4), 401 - 7
Construction of Neisseria meningitidis strains carrying multiple chromosomal copies of the porA gene for use in the production of a multivalent outer membrane vesicle vaccine; van der Ley P et al.; Starting with Neisseria meningitidis strain H44/76, a set of strains was constructed for use in production of a multivalent outer membrane vesicle vaccine . The aim was to remove unwanted outer membrane components and at the same time to improve the range of protection . This was accomplished through transformation with plasmid constructs made in Escherichia coli and their homologous recombination into the meningococcal chromosome . Deletion of the cps locus resulted in loss of expression of the group B capsular polysaccharide as well as the lacto-N-neotetraose structure in lipopolysaccharide . Deletion of the porB gene abolished expression of the class 3 outer membrane protein . Additional copies of the porA gene, encoding the immunodominant class 1 outer membrane protein, were inserted into one of the opa genes and into the rmpM gene encoding the class 4 outer membrane protein . This construction was done with three sets of porA alleles, resulting in three trivalent strains, each of which expressed a different combination of class 1 epitopes.

Acta Paediatr, 1995 Mar, 84(3), 342 - 5
Recrudescence and relapse of meningococcal meningitis and septicaemia; Nielsen PE et al.; Three cases of recrudescence and relapse of Neisseria meningitidis group B meningitis and septicaemia are reported . The recrudescence and relapses could not be explained by infectious foci, increased bacterial penicillin resistance or immunological defects . As a supplement to antibiotic treatment, all three patients received corticosteroids for the initial 2 days of treatment, and this may have contributed to the unusual course of the disease in our patient.

Epidemiol Mikrobiol Imunol, 1995 Mar, 44(1), 9 - 14
{Evaluation of the effectiveness of targeted vaccination with the meningococcal polysaccharide A and C vaccine in one location in the Czech Republic}; Krizova P et al.; In the Czech Republic where meningococcal disease occurred only sporadically for a very long period and Neisseria meningitidis B prevailed, the use of a meningococcal polysaccharide vaccine was never indicated . This situation changed in 1993 when a new clone of Neisseria meningitidis C:2a:P1.2(P1.5) appeared in the Czech Republic, found to be responsible for a new epidemiological and clinical situation . The disease caused by this new clone is more serious, showing a high fatality rate (20%) and frequently an atypical clinical course . In May 1993, the highest age-specific incidence in the most affected locality was established in the age group of 15-19 years (52.1/100,000), while in the whole Czech Republic the respective figure was 2.4 . A vaccination campaign focusing on the most affected age group started in this locality at the beginning of June 1993, using a polysaccharide meningococcal vaccine A+C (Merieux) . During two weeks 6191 students of the age group of 15-19 years were vaccinated, i.e . 96% of all students of this age group, 64.5% of the population 15-19 years old and 5.6% of the whole population of this locality . This age targeted vaccination prevented the spread of the meningococcal invasive disease caused by Neisseria meningitidis C in this locality . The decrease in morbidity in this locality is statistically highly significant (p < 0.001) . In another affected locality, where vaccination was not age targeted and showed a very low coverage, the incidence of the invasive disease caused by Neisseria meningitidis C did not decrease . During the following period (1993-1994) the new meningococcal clone spread to all regions of the Czech Republic . Active surveillance of meningococcal invasive disease has been conducted with the aim to recognize as early as possible an emerging epidemiological indication for targeted vaccination.

Mol Microbiol, 1995 Mar, 15(6), 1001 - 7
Interspecies recombination in nature: a meningococcus that has acquired a gonococcal PIB porin; Vazquez JA et al.; A vaginal isolate of Neisseria has been reported to resemble Neisseria meningitidis in biochemical characteristics but to react with serological reagents that are specific to the PI porin from Neisseria gonorrhoeae . We have confirmed that this isolate has the biochemical attributes of a meningococcus and have shown that it clusters among meningococcal isolates on a dendrogram based on isoenzyme variation within housekeeping enzymes from populations of N . meningitidis and N . gonorrhoeae . Furthermore, the sequences of the fbp and adk genes were typical of those of N . meningitidis and were distinct from those of N . gonorrhoeae . However, the porB gene was very similar to the por genes of N . gonorrhoeae isolates that express the PIB class of outer-membrane porin (differing from one gonococcal por allele at only a single nucleotide site), and was clearly distinct from the porB genes of N . meningitidis . The isolate therefore appears to be a typical meningococcus, except that its porB gene has been replaced with the por gene from a gonococcus.

Gac Sanit, 1995 Mar-Apr, 9(47), 84 - 90
{An evaluation of the epidemiological surveillance system for infectious diseases in the Barcelona Olympic Games of 1992}; Panella H et al.; Due to the 1992 Barcelona Olympic Games some modifications were introduced in the epidemiologic surveillance system for infectious diseases in place in the city, in order to expand its coverage and shorten its timeliness in detecting outbreaks and investigating cases . These modifications were introduced for a group conditions (hepatitis, meningococcal disease, legionnaire's disease and food outbreaks), selected on the basis of incidence, time of the year, previous experience in other settings, and likelihood of outbreak occurrence . In the June-August 1992 period (Olympic period), no increases in the incidence of selected conditions were observed when compared to the same period in 1986 to 1991 . Major changes were observed in the source of food outbreak reporting, with a large increase in outbreaks reported by emergency room departments . There was an increase in the number of domestic foodborne outbreaks and a reduction in those related with restaurants . Timeliness in the detection of cases was shortened . The use of similar modifications can be useful for epidemiologic surveillance systems in other comparable settings or occasions.

MMWR Morb Mortal Wkly Rep, 1995 Feb 24, 44(7), 121 - 4
Serogroup B meningococcal disease--Oregon, 1994.
Meningococcal meningitis and carriage in western Zaire: a hypoendemic zone related to climate?
Department of Medical Microbiology, University of LiverpoolAn analysis of bacteria recovered from cerebrospinal fluid over a 16-year period at a rural hospital in western Zaire showed that Neisseria meningitidis accounted for only five (2.2%) isolates . A survey of naso-pharyngeal colonisation with N . meningitidis in 378 healthy children was undertaken to distinguish whether this low frequency was due to lack of carriage or, by inference, lack of the co-factors necessary to permit invasive disease . N . meningitidis was recovered from only three (0.78%) of the children . All isolates were non-typable strains of low pathogenicity . A review of studies examining the aetiology of bacterial meningitis and the geographical location of epidemics of meningococcal meningitis in and around Zaire reveals a 'hypoendemic zone', the limits of which correlate well with the area in which mean absolute humidity remains above 10 g m-3 of air throughout the year . Continuous high absolute humidity appears to reduce the transmission of meningococci.

JAMA, 1995 Feb 1, 273(5), 390 - 4
The changing epidemiology of invasive meningococcal disease in Canada, 1985 through 1992 . Emergence of a virulent clone of Neisseria meningitidis; Whalen CM et al.; OBJECTIVE--To describe the occurrence of invasive meningococcal disease (IMD) in Canada with respect to demographic variables and characteristics of the isolated strains of Neisseria meningitidis . DESIGN--National surveillance case series . SETTING--Canada, 1985 through 1992 . OUTCOME MEASURES--Morbidity and mortality . MAIN RESULTS--The incidence of IMD averaged 1.38 per 100,000 person-years, with considerable regional variation . In 1988, serogroup C organisms became more common, with one strain of the electrophoretic type 37 (ET-37) complex of N meningitidis, termed ET-15, the predominant group C strain identified . With the increase in group C disease, a greater proportion of cases were older than 5 years . By 1991, ET-15 was the most common strain identified in most parts of the country . Electrophoretic type 15 had a case fatality of 17.8% vs 8.1% for all other IMD (P < .001) . Among cases 20 years and older the case fatality for ET-15 was 22.4% . CONCLUSIONS--The group C, ET-15 strain of N meningitidis, first identified in Canada, was more virulent than other prevalent strains during this period . Active surveillance, rapid identification, and typing of N meningitidis will assist public health decision making in the control of emerging strains.

JAMA, 1995 Feb 1, 273(5), 383 - 9
Serogroup C meningococcal outbreaks in the United States . An emerging threat; Jackson LA et al.; OBJECTIVE--Multiple outbreaks of serogroup C Neisseria meningitidis have recently been reported from diverse areas of the United States . To better define the characteristics of this increasingly important problem, we reviewed data on all known serogroup C outbreaks in the United States from January 1980 through June 1993 . DATA SOURCES--MEDLINE searches, Centers for Disease Control and Prevention records, state health department officials, infectious disease experts, and the meningococcal vaccine manufacturer . DEFINITION OF AN OUTBREAK--Three or more cases of serogroup C meningococcal disease within a 3-month period, either among members of a community or persons attending a single school or other institution, for which those cases represented an attack rate of at least five per 100,000 population . RESULTS--Twenty-one outbreaks of serogroup C meningococcal disease were identified; eight occurred since 1991 . In 1992 and the first half of 1993, approximately 180,000 doses of vaccine were administered for outbreak control, compared with approximately 34,000 doses from 1980 to 1991 . Approximately 50% of community-outbreak cases were between the ages of 5 and 24 years, compared with only 19% of sporadic serogroup C cases (P < .001) . Subtyping of patient isolates indicates that outbreaks are clonal; however, at least five distinct but closely related strains have caused recent outbreaks . CONCLUSIONS--Serogroup C outbreaks are occurring more frequently in the United States . The effectiveness of preventive measures depends on early recognition; therefore, physicians should promptly report all cases of suspected meningococcal disease, and the causative serogroup should be established for every case.

Clin Ter, 1995 Feb, 146(2), 153 - 6
Candida chorioretinitis in meningococcal meningitis; Maddaluno R et al.; A case of Candida chorioretinitis in a patient suffering from meningococcal meningitis, admitted to the Infectious Disease Department of Frosinone Hospital, Italy, is reported . Five days after the onset of meningitis during antibiotic and cortisone treatment the patient experienced oropharyngeal candidiasis, ocular pain and blurring of vision; two days later positive scotoma appeared . Ophthalmoscopic examination revealed probable Candida chorioretinitis . Treatment with intravenous fluconazole at high doses was employed with complete recovery of the right eye, while visual acuity of the left eye was 2/10 . The use of long-term fluconazole at the doses reported, commonly employed in the treatment of systemic mycoses, improves prognosis.

Cent Afr J Med, 1995 Feb, 41(2), 54 - 9
Acute bacterial meningitis in Enugu, Nigeria . 1 April 1989 to 31 March 1993; Ozumba UC; A total of 84 cases of meningitis confirmed by isolation of the organisms at the University of Nigeria Hospital (UNTH) Enugu, Nigeria between 1 April 1989 and 31 March 1993 are presented . The cases are analysed by diagnosis, seasonal distribution, age and sex distribution and age specific case fatality rate . The most common type of meningitis was pneumococcal meningitis 32 cases, followed by coliform meningitis 31 cases and meningococcal meningitis, six cases . Other bacterial causes of meningitis accounted for 15 cases . The majority of cases occurred in infants, followed by children, with all cases occurring sporadically . Mortality was high with Streptococcus pneumoniae having the highest case fatality rate of 28.13 pc followed by coliforms, 25.78 pc . Fifty pc of the patients had pre-medication before presentation at the hospital, and many of the patients could not receive appropriate therapy because they were unable to afford the cost of the drugs . This probably contributed to the high mortality.

Mol Microbiol, 1995 Feb, 15(3), 531 - 41
The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence; Stojiljkovic I et al.; The Neisseria meningitidis haemoglobin receptor gene, hmbR, was cloned by complementation in a porphyrin-requiring Escherichia coli mutant . hmbR encodes an 89.5 kDa outer membrane protein which shares amino acid homology with the TonB-dependent receptors of Gram-negative bacteria . HmbR had the highest similarity to Neisseria transferrin and lactoferrin receptors . The utilization of haemoglobin as an iron source required internalization of the haemin moiety by the cell . The mechanism of haemin internalization via the haemoglobin receptor was TonB-dependent in E . coli . A N . meningitidis hmbR mutant was unable to use haemoglobin but could still use haemin as a sole iron source . The existence of a second N . meningitidis receptor gene, specific for haemin, was shown by the isolation of cosmids which did not hybridize with the hmbR probe, but which were able to complement an E . coli hemA aroB mutant on haemin-supplemented plates . The N . meningitidis hmbR mutant was attenuated in an infant rat model for meningococcal infection, indicating that haemoglobin utilization is important for N . meningitidis virulence.

FEMS Immunol Med Microbiol, 1995 Feb, 10(3-4), 185 - 9
Epidemiological evaluation of Neisseria meningitidis serogroup B by pulsed-field gel electrophoresis; Yakubu DE et al.; Genomic DNA from 25 strains of serogroup B Neisseria meningitidis was subjected to pulsed-field gel electrophoresis (PFGE) after digestion with Spe I . N . meningitidis genomic DNA displayed considerable diversity . The diversity we observed among these strains was stable and included isolates from an outbreak that were phenotypically identical . This confirms the value of macrorestriction profiling and PFGE in providing epidemiologically stable strain markers for typing meningococci.

APMIS, 1995 Feb, 103(2), 147 - 53
Strain differentiation of Neisseria meningitidis by small-fragment restriction endonuclease analysis (SF-REA); Mylvaganam H et al.; Following an outbreak involving 3 cases of serogroup B meningococcal disease in a rural part of Western Norway, 2 clinical and 99 carrier isolates of Neisseria meningitidis were examined by small-fragment restriction endonuclease analysis (SF-REA) using EcoRI, to determine its potential for strain differentiation . SF-REA characterized all isolates and provided reproducible results with acceptable inter-clonal differentiation . The results of SF-REA correlated well with those of serological typing and were used to determine clonal diversity and prevalence of invasive strains among the carrier isolates . SF-REA was also useful in demonstrating acquisition of a new carrier strain after eradication of the initial strain by ofloxacin . Thirty-one different restriction patterns/pattern complexes were recognized among the 101 isolates . The two clinical isolates had identical restriction patterns and showed > or = 90% similarity to those of six carrier isolates . In three out of six apparent treatment failures, successful eradication of the original strain by ofloxacin was demonstrated by SF-REA . SF-REA proved valuable in strain differentiation of Neisseria meningitidis, complemented serology, and characterized all isolates which could not be typified by serology.

J Clin Microbiol, 1995 Feb, 33(2), 458 - 62
Typing Neisseria meningitidis by analysis of restriction fragment length polymorphisms in the gene encoding the class 1 outer membrane protein: application to assessment of epidemics throughout the last 4 decades in China; Zhu P et al.; A typing method was developed for Neisseria meningitidis serogroup A by analysis of restriction fragment length polymorphisms (RFLP) of the class 1 outer membrane protein gene (porA) . By using appropriate primers, an approximately 1,116-bp fragment of the porA gene was amplified by PCR and then was digested with the restriction endonuclease MspI . The digestion products were separated on 10% polyacrylamide gels and were stained with silver . One hundred three clinical isolates of group A N . meningitidis from 17 provinces of China collected over a 26-year period were analyzed . Results of MspI-generated RFLP profiles of PCR-amplified porA genes were compared with those obtained by conventional serosubtyping . There was a band of about 400 bp common to all strains examined, and the 103 strains of serogroup A resulted in 22 unique RFLP patterns . The differences in bands could be observed mainly in the range of 120 to 280 bp . The smaller fragments were useful in distinguishing meningococci with the same serosubtype . Three epidemic periods were characterized by the presence of three distinct genotypes (a1, a2, and a3), accounting for 74.5% of the strains examined (3.88, 26.21, and 44.66%, respectively) . Three predominant RFLP patterns were correlated epidemiologically with cycles of epidemic meningococcal meningitis and were well-matched to the predominant serosubtypes (P1.9, P1.7, 10, and P1.9) that presented at the same prevalence cycles . The genotyping yielded information that allowed strains from one epidemic to be distinguished from those from another that would have been indistinguishable if only serotyping and serosubtyping were available . Therefore, the PCR-RFLP typing method was very useful in the epidemiologic investigation of group A meningococcal meningitis.

Microb Pathog, 1995 Feb, 18(2), 97 - 107
Whole blood model of meningococcal bacteraemia--a method for exploring host-bacterial interactions; Ison CA et al.; An ex vivo whole blood model of meningococcal bacteraemia was developed to examine the total bactericidal activity of blood . Using a single defined donor and strains belonging to serogroups A, B and C and an unencapsulated strain, we demonstrated that the bactericidal mechanisms operating in whole blood varied with anticoagulant, serogroup and bacterial growth conditions . The choice of anticoagulant had a major effect on the survival of the serogroup A strain with 94% (SEM 7.6) survival in citrated blood compared to 19.7% (SEM 19.6) survival in heparinised blood after 60 min incubation . The serogroup C strain showed enhanced survival when grown in liquid medium compared to growth on solid medium (73.5%, SEM 7.5, and 8.2%, SEM 3.1, respectively, in citrated blood after 60 min) . The pattern of survival of serogroup B and the unencapsulated strain were largely unaffected by these variables . Comparison with cell free conditions allowed the contribution of cellular components in meningococcal killing to be determined . Secreted levels of tumour necrosis factor and neutrophil elastase secreted during whole blood assays did not correlate with bacterial growth or viability indicating a lack of relationship between killing and activation of phagocytes.

Diagn Microbiol Infect Dis, 1995 Feb, 21(2), 115 - 7
Evaluation of the Etest for penicillin susceptibility testing of Neisseria meningitidis; Gomez-Herruz P et al.; Susceptibility to penicillin of 30 strains (one isolate per patient) of Neisseria meningitidis isolated from blood (N = 19) or cerebrospinal fluid (N = 11) was studied by two methods . Minimum inhibitory concentrations (MICs) obtained with the Etest were compared to those obtained by the National Committee for Clinical Laboratory Standards agar dilution method . Twenty meningococci (67%) relatively resistant to penicillin were identified by both methods . The mean MIC from the reference method was 0.32 micrograms/ml (range, 0.2-1) and by the Etest method was 0.35 micrograms/ml (range, 0.19-1.25) . All MICs obtained by the Etest method were within one dilution of the MICs obtained by the reference method . Because of the increase in penicillin MIC of meningococcal isolates in Spain, we evaluated the performance of the Etest as an alternative method for penicillin-susceptibility testing of N . meningitidis . The Etest is a simple and accurate method for determining the susceptibility of N . meningitidis to penicillin.

FEMS Microbiol Lett, 1995 Jan 15, 125(2-3), 255 - 63
Identification and characterization of specific sequences encoding pathogenicity associated proteins in the genome of commensal Neisseria species; Wolff K et al.; The distribution of distinct sequences in pathogenic and commensal Neisseria species was investigated systematically by dot blot analysis . Probes representing the genes of Rmp, pilin and IgA1 protease were found to hybridize exclusively to the chromosomal DNA of the pathogenic species, Neisseria gonorrhoeae and/or Neisseria meningitidis . In contrast, specific sequences for the genes of the porin protein Por and the opacity protein (Opa) were also detected in a panel of commensal Neisseria species such as N . lactamica, N . subflava, N . flava, N . mucosa and N . sicca . Using opa-specific oligonucleotides as probes in chromosomal blots, the genomes of the commensal Neisseria species show a totally reduced repertoire of cross-hybridizing loci compared to the complex opa gene family of N . gonorrhoeae . DNA sequence analysis of one opa-related gene derived from N . flava and N . sicca, respectively, revealed a large degree of homology with previously described gonococcal and meningococcal genes, e.g., a typical repetitive sequence in the leader peptide and the distribution of the hypervariable and conserved regions . This observation, together with the finding, that the gene is constitutively transcribed, leads to the assumption that some of the commensal Neisseria species may have the potential for the expression of a protein harboring similar functions as the Opa proteins in pathogenic Neisseriae.

J Clin Apheresis, 1995, 10(4), 171 - 7
Intensive blood and plasma exchange for treatment of coagulopathy in meningococcemia; Churchwell KB et al.; Eight pediatric patients with fulminant meningococcemia, purpura, and disseminated intravascular cogulation who by multiple prognostic scoring systems were anticipated to have a poor outcome underwent intensive plasma exchange (IPE) or whole blood exchange (WBE) in addition to standard medical therapy . IPE/WBE was initiated shortly after admission with a mixture of both fresh frozen plasma and cryoprecipitate as the replacement solution . All IPE procedures were performed using a continuous flow system and a red cell prime . The mean fibrinogen level increased from 62 to 192 mg/dl, the prothrombin time (PT) decreased from a mean of 32.4 seconds to 15.1 seconds, and the mean activated partial thromboplastin time (APTT) decreased from 89.5 seconds to 40.1 seconds following completion of the initial IPE/WBE . There was a corresponding improvement in all coagulation factor levels but only slight improvement in antithrombin III (ATIII) and protein C levels . Seven of eight patients survived (87.5%) their initial presentation with the sole early death attributed to meningitis with cerebral edema . Mean fluid balance after the procedure was +10.8 +/- 5.87 cc/kg . There were no significant bleeding or cardiovascular complications during the procedure . There was no clinical or radiographic evidence of fluid overload after the procedure . This experience demonstrates that IPE/WBE may be conducted safely in critically ill, unstable pediatric patients and is effective in rapidly improving coagulopathy without fluid overload.

Scand J Infect Dis, 1995, 27(5), 527 - 8
Fatal rickettsial meningitis in Hong Kong: a need for rapid laboratory diagnosis; Young RP et al.; A 22-year-old Chinese male, investigated elsewhere for fever and myalgia, was transferred to our hospital drowsy, unresponsive to commands and with a petechial rash . Partially treated meningococcal meningitis was suspected and high-dose antibiotics were immediately started . Rising Weil-Felix titres occurred too late for anti-rickettsial therapy to prevent a fatal outcome . Subsequent specific serology showed rising titres against Rickettsia conori . The desirability of more rapid and reliable methods of laboratory diagnosis of rickettsial infection is evident.

Can J Anaesth, 1995 Jan, 42(1), 64 - 8
Sonoclot coagulation analysis and plasma exchange in a case of meningococcal septicaemia; Schott U et al.; On the basis of a patient with fulminant meningococcaemia and severe disseminated intravascular coagulation (DIC) syndrome, the diagnostic potential of a clot impedance test - Sonoclot coagulation analysis - was used to evaluate plasma exchange . A 17-yr-old girl was treated for a fulminant infection with Neisseria meningitidis in our intensive care unit . She developed severe DIC . Whereas platelet administration caused immediate arterial oxygen desaturation necessitating ventilatory support, plasma exchange improved pulmonary and mental function . Three separate exchanges all improved haemostasis . Sonoclot analysis was used together with routine coagulation analyses to evaluate this DIC treatment . Sonoclot signs, such as lack of the shoulder and peak, prolonged shoulder-peak interval and peak time predicted clinical bleeding manifestations (haematuria, haemoptysis, epistaxis) and were improved by platelet transfusion and plasma exchange . Plasma exchange was successful even at a very low platelet count of < 23 x 10(9).L-1 . Sonoclot coagulation analyses were normalised several days before routine coagulation analyses . The Sonoclot gave additional information to routine coagulation studies, correctly indicated insufficient haemostasis and predicted a positive outcome . Also, plasma exchanges and platelet transfusions could be controlled in the management of DIC.

Isr J Med Sci, 1995 Jan, 31(1), 54 - 8
Meningococcal disease in the Israel Defense Force: epidemiologic trends and new challenges; Grotto I et al.; To determine recent trends in its epidemiology and the need to reconsider prophylactic interventions, meningococcal disease in the Israel Defense Force (IDF) from 1975 through 1993 was studied . All cases of meningitis or meningococcemia were included . A considerable increase in the number of cases has been observed since 1991, with serogroup C becoming predominant (76% of cases) since then . Serogroup Y was the second most frequent serogroup during this period, while serogroup B, predominant in the civilian population of Israel, was rare . Most cases occurred during the first 6 months of military service . Seasonality was important, with most of the cases occurring between December and March, although a small summer peak was also noted . Since 1992, three small clusters of meningococcal disease were encountered in the IDF, for the first time, with all cases caused by group C meningococci . In one cluster, the emergence of rifampicin resistance resulted in failure of chemoprophylaxis . The rise in group C and Y cases since 1991, and the occurrence of rifampicin resistance, necessitate considering meningococcal vaccines and new antimicrobial agents for prophylaxis.

Infect Immun, 1995 Jan, 63(1), 160 - 7
Neisserial porins inhibit human neutrophil actin polymerization, degranulation, opsonin receptor expression, and phagocytosis but prime the neutrophils to increase their oxidative burst; Bjerknes R et al.; Porins are trimeric proteins that constitute water-filled pores that allow transmembrane diffusion of small solutes through the outer membrane layer of gram-negative bacteria . The porins are capable of inserting into the membranes of eucaryotic cells, and in the present study we have examined the in vitro effects on neutrophil functions of the following purified porins: meningococcal outer membrane protein classes 1 and 3 and gonococcal outer membrane protein 1B (P1B) . The neisserial porins inhibited human neutrophil chemoattractant-induced actin polymerization and degranulation of both primary and secondary granules . The neutrophil expression of immunoglobulin G (IgG) Fc receptors II (Fc gamma RII; CDw32) and III (Fc gamma RIII; CD16), as well as the activation-dependent downregulation of Fc gamma RIII, were reduced by the meningococcal and gonococcal porins . The neisserial porins impaired the upregulation of complement receptors 1 (CD35) and 3 (CD11b) and inhibited the phagocytic capacity of neutrophils, as evaluated by the uptake of meningococci (strain 44/76) in the presence of patient serum containing known amounts of IgG against meningococcal porins . The porins also primed neutrophils to increase their intracellular hydrogen peroxide production in response to FMLP, whereas no such priming was observed if the neutrophil protein kinase C was stimulated directly with phorbol myristate acetate . The neisserial porins influenced neutrophil functions in a time- and concentration-dependent manner . The meningococcal class 1 outer membrane protein and the gonococcal P1B tended to alter neutrophil functions more than the meningococcal class 3 protein . Thus, the neisserial porins inhibited human neutrophil actin polymerization, degranulation, opsonin receptor expression, and phagocytosis but primed the neutrophils to increase their oxidative burst . It remains to be determined whether these in vitro observations reflect mechanisms that may be of importance for the interaction between neutrophils and Neisseria species in vivo.

J Infect Dis, 1995 Jan, 171(1), 229 - 32
High levels of interleukin-10 during the initial phase of fulminant meningococcal septic shock; Derkx B et al.; Interleukin (IL)-10 has an important antiinflammatory effect by inhibiting endotoxin-induced production of proinflammatory cytokines, such as tumor necrosis factor-alpha and IL-1 . Since both cytokines are produced in massive amounts during fulminant meningococcal septic shock and are associated with severity of disease, IL-10 was measured in plasma samples of 25 consecutive children with fulminant meningococcal septic shock shortly after admittance to a pediatric intensive care unit . High levels of IL-10 (median, 6021 pg/mL; range, 137-24,600) were found in surviving patients (median, 1268 pg/mL; range, 137-24,600) and in those who died (median, 9915 pg/mL; range, 3996-14,100) . IL-10 levels correlated weakly (r = .38; P = .055) with severity of disease as measured by the Glasgow meningococcal septicemia prognostic score . The findings indicate that IL-10 is produced in massive amounts in the initial phase of fulminant meningococcal septic shock.

J Infect Dis, 1995 Jan, 171(1), 113 - 21
The effect of variations in the expression of pili on the interaction of Neisseria meningitidis with human nasopharyngeal epithelium; Rayner CF et al.; Bacterial adherence is essential to colonization of the nasopharynx by Neisseria meningitidis, and pili may facilitate adherence . Scanning electron microscopy and immunogold labeling were used to study the interaction of 2 piliated and 1 nonpiliated variant of N . meningitidis with nasopharyngeal mucosa in an adenoid organ culture system with an air-mucosal interface . Meningococcal infection caused epithelial damage, loss of ciliated epithelium, and ciliary disorganization, which progressed with time and were greater with the piliated strains . Pili increased adherence of meningococci to the mucosa, and there was tropism of piliated strains for nonciliated cells containing microvilli, damaged epithelium, and sites of cell separation . Bacterial adherence was associated with a change in the appearance of the microvilli.

Scand J Infect Dis, 1995, 27(1), 75 - 6
Cranial nerve palsies and cerebral infarction in a young infant with meningococcal meningitis; Chiu CH et al.; A previously healthy 30-day-old male infant became ill with fever, poor activity, and refusal to feed for 2 days . A cerebrospinal fluid examination revealed 7.15 x 10(8) leukocytes/l with 72% neutrophils, protein 4.6g/l, and glucose 7 mg/dl . Neisseria meningitidis was isolated from the blood and cerebrospinal fluid . On the fourth day of hospitalization, the baby was found to have left oculomotor and facial palsies, which resolved gradually . He was treated with intravenous penicillin for 2 weeks . A repeat CSF examination revealed a high persisting protein level of 2.9 g/l and a computerized tomographic brain scan revealed a cerebral infarction in the bilateral frontal lobes . The treatment was extended to 4 weeks . No relapse of the infection was noted . This is the first case report of an infant with meningococcal meningitis complicated by cranial nerve palsies and cerebral infarction . This and previous reports, show that meningococcal meningitis at an extremely young age is associated with a greater risk of developing neurological complications.

Vaccine, 1995 Jan, 13(1), 112 - 8
Considerations on the use of Neisseria meningitidis class 5 proteins as meningococcal BC vaccine components; Sacchi CT et al.; This investigation was carried out to evaluate the importance of individual meningococcal surface class 5 protein with respect to antibody induction and its functional activity . Two groups of mice were immunized with two vaccine preparations differing in the presence or absence of class 5 protein . The ELISA results show that both vaccines were immunogenic and elicited mainly IgG antibodies against the major classes of meningococcal surface proteins, and the absence of class 5 protein in the vaccine produced a significant change in the overall units ml-1 of antibodies against the homologous strain . The infant rat model and the bactericidal assay were used to evaluate the functional antibody activity . Our results showed that (1) even using two different challenge doses (10(6) and 10(7) bacteria/animal), mortality could not be detected when followed up at 48 h; (2) there was protection as determined by the infant rat model and bactericidal activity using sera from both vaccinated groups; (3) there were no differences in the bactericidal titres between these groups; (4) in the infant rat model there were no differences in the index of bacteraemia among the infected animals (counts ml-1 of blood); and (5) there were differences in the incidence of bacteraemia . This is the first evidence that some immunological differences in the vaccine response could be attributed to the absence of class 5 protein by using infant rat model but not by using the bactericidal assay.

Klin Lab Diagn, 1995 Jan-Feb, (1), 26 - 9
{Immune bacteriolysis reaction in the assessment of immunological effectiveness of serogroup B meningococcal vaccine}; Golovina LI et al.; The immunological efficacy of serogroup B meningococcal protein-polysaccharide vaccine was studied in newly developed immune bacteriolysis test . Serogroup B meningococcus strains had different sensitivities to the bactericidal effects of immune sera . A single injection of the vaccine caused an induction of bactericidal antibodies to meningococcus vaccinal strain . Three weeks after vaccination 77.7% of the vaccines developed an appreciable increase of the titers of bactericidal antibodies to the homologous strain of meningococcus . The concentration of bactericidal antibodies to strain 2394 differing from the homologous strain by its serotype did not increase . In the controls no changes in the titers of bactericidal antibodies to both strains of meningococcus were observed, the level of antibodies being the same as that before vaccination in the group of subjects immunized with B vaccine; this proves the specificity of the immunizing effect to serogroup B meningococcus vaccinal strain (No 125).

Thromb Haemost, 1995 Jan, 73(1), 15 - 20
Coagulation activation and tissue necrosis in meningococcal septic shock: severely reduced protein C levels predict a high mortality; Fijnvandraat K et al.; In 35 consecutively admitted children (mean age: 4.3 years) with a clinical diagnosis of meningococcal septic shock (MSS), activation of the coagulation and fibrinolytic pathways was evaluated directly at admittance to the paediatric intensive care unit (ICU) . The association of clinical signs and haemostatic abnormalities was assessed . All patients had signs of extensive activation of the coagulation system . The 28-day mortality was 26% . Protein C activity was strongly reduced, especially in non-survivors in whom it was significantly lower than in survivors (5% versus 23%; p < 0.0001) . There was a strong negative correlation between protein C activity and the mean size of the skin lesions (r = -0.71, p < 0.001) . These results suggest that an acquired protein C deficiency in MSS is related to the pathogenesis of purpura fulminans . Furthermore, no increase in C4b-binding protein (C4BP) and no decrease in the ratio free protein S/total protein S was observed, suggesting that a deficiency of free protein S as a result of increased C4BP does not play a pathogenetic role in meningococcal septic shock.

Postgrad Med J, 1995 Jan, 71(831), 42 - 3
Guillain-Barré syndrome following meningococcal meningitis; Puri V et al.; A case of Guillain-Barre syndrome following meningococcal meningitis is reported . The diagnosis was made on clinical grounds and the results of electrophysiological studies . The patient recovered spontaneously . Guillain-Barre syndrome following meningococcal infection has not to our knowledge been reported previously.

J Clin Microbiol, 1995 Jan, 33(1), 53 - 7
Meningococcal infections in the Province of Québec, Canada, during the period 1991 to 1992; Ringuette L et al.; A total of 234 strains of Neisseria meningitidis obtained from hospitalized patients living in the province of Quebec during the period 1991 to 1992 were characterized according to their serogroup, serotype, subtype, electrophoretic type, and antimicrobial susceptibility . All these strains were recovered from sterile body fluids, except for one strain that was isolated postmortem from a cutaneous lesion . For both years, serogroup C was the most prevalent (69.7%), followed by serogroup B (27.4%) . Serotype 2a represented 80.3% of serogroup C isolates, and P1.2 was the most common subtype associated with this serotype . Clone ET 15 accounted for 76.5% of serogroup C isolates and 90.0% of serotype 2a strains . Although meningococcal disease occurred mostly in children under the age of 5 (9.7 cases per 100,000 children), with a peak incidence for children under 1 (20.3 cases per 100,000 children), most fatalities occurred among teenagers (12 to 19 years old) . The total fatality rate was 11.5%, and serogroup C strains were responsible for 88.9% of these fatalities . Thirteen strains had a reduced susceptibility to penicillin G, and 28 strains were resistant to sulfadiazine . One strain was resistant to both rifampin and sulfadiazine and showed a reduced susceptibility to penicillin G.

Rev Inst Med Trop Sao Paulo, 1995 Jan-Feb, 37(1), 1 - 5
Monoclonal antibody to serotype 17 of Neisseria meningitidis and their prevalence in Brazilian states; Sacchi CT et al.; Neisseria meningitidis are gram-negative diplococci responsible for cases of meningococcal disease all over the world . The epidemic potential of N . meningitidis serogroup B and C is clearly a function of their serotype antigens more than of their capsular polysaccharides . Until recently, hiperimmune sera were used to detect typing antigens on the bacteria . The advent of monoclonal antibodies (MAbs) offered the opportunity to eliminate many of the cross-reactions and have improved the accuracy and reproducibility of meningococcal serotyping . We have produced a MAb to the outer membrane protein of the already existent serotype 17 that have been detected by the use of hiperimmune rabbit sera . The prevalence of this serotype epitope is low in the Brazilian strains . By using the MAb 17 we could not decrease the percentage of nontypeable serogroup C strains . However, there were a decreasing in nontypeable strains to 13% into serogroup B strains and to 25% into the other serogroups.

Rev Pneumol Clin, 1995, 51(2), 90 - 2
{Meningococcal pneumonia}; Bourlaud I et al.; Meningococci can cause primary bacterial pneumonia . The clinical picture is non-specific and the clinical course leads to meningeal infection . Diagnosis is based on isolation of Neisseria meningitidis in lung samples . Outcome is usually favourable.

Retina, 1995, 15(3), 213 - 9
Endogenous endophthalmitis simulating retinoblastoma . The 1993 David and Mary Seslen Endowment Lecture; Shields JA et al.; BACKGROUND: Among conditions that can simulate retinoblastoma, endogenous endophthalmitis is quite rare . METHODS: Case records of six children with unusual forms of endogenous endophthalmitis, all of whom were referred to the authors because retinoblastoma was a strong diagnostic consideration, were reviewed . The clinical features that may help differentiate atypical endophthalmitis from retinoblastoma were investigated . RESULTS: The final diagnosis in these cases included idiopathic subretinal abscess, streptococcal endophthalmitis, idiopathic retinovitreal abscess, cytomegalovirus endophthalmitis, Candida endophthalmitis, and meningococcal endophthalmitis . All of the affected children presented primarily with ocular findings without serious systemic infection . Although these conditions closely simulated retinoblastoma, they were more likely to have signs of concurrent or prior inflammation . CONCLUSION: Differentiation between infectious conditions and retinoblastoma can sometimes be difficult, but clues as to the diagnosis can be obtained from careful clinical examination.

Hum Antibodies Hybridomas, 1995, 6(2), 42 - 6
Comparison of three human-murine heteromyeloma cell lines for formation of human hybridomas after electrofusion with human peripheral blood lymphocytes from meningococcal cases and carriers; Delvig AA et al.; Peripheral blood lymphocytes from meningitis patients and healthy meningococcal carriers were fused by electrofusion with the three human-murine heteromyeloma cell lines CB-F7, K6H6B5 and H7NS . 934 hybridomas producing human immunoglobulins were obtained in 30 fusions . Heteromyeloma K6H6B5 yielded a significantly higher proportion of hybridomas producing IgG antibodies than did the two other cell lines . CB-F7 and K6H6B5 yielded comparable numbers of hybridomas whose supernatants reacted with homologous bacteria, whereas the cell line H7NS was less efficient.

Epidemiol Mikrobiol Imunol, 1994 Dec, 43(4), 183 - 7
{The new epidemiologic situation in the Czech Republic caused by the C:2a:P1.2 (P1.5) strain of meningococci}; Krizova P et al.; A new epidemiological situation for invasive meningococcal disease developed in the Czech Republic in 1993 . The investigation of meningococcal noncapsular antigens revealed that the new strain Neisseria meningitidis C:2a:P1.2 (P1.5) is the causative agent . This strain has never been found in the Czech Republic before, at least not since 1973 (Czech meningococci have been sero/subtyped since) . The investigation of the relationships by ET-typing revealed that this Neisseria meningitidis C:2a:P1.2 (P1.5) belongs to the ET-37 clone . In spring 1993 this new meningococcal clone caused an unusual increase of morbidity in two districts in one region of the Czech Republic and during the next winter/spring season (1993/1994) it spread to all regions of the country . This new strain causes severe and frequently atypical clinical manifestations, with the highest morbidity and fatality rates in the age group of 15-19 years (20% fatality in 1993).

Epidemiol Mikrobiol Imunol, 1994 Dec, 43(4), 180 - 2
{Indications for vaccination against invasive meningococcal disease in Olomouc}; Janout V et al.; Problems connected with the decision about indication of vaccination in connection with the increase of invasive meningococcal disease are discussed . The epidemiological situation in the Olomouc district, where a local outbreak of invasive meningococcal diseases occurred, is briefly described and factors in favour of and against the indication of vaccination are discussed.

Biologicals, 1994 Dec, 22(4), 323 - 7
Epidemiological views into possible components of paediatric combined vaccines in 2015; Eskola J; Efforts to develop combined vaccines for childhood immunization schedules will during the next years focus on combined administration of the existing vaccines which have already shown their impact . First candidate components for more wide-spectrum combinations could be the new antigens against severe invasive infections caused by encapsulated bacteria . Multivalent pneumococcal and meningococcal group A and C conjugate vaccines are already in clinical trials, and the same is true of the first candidates for the meningococcal group B vaccine . Pneumococcal conjugate vaccines are also important in prevention of a large variety of respiratory infections . Since viruses are important causative agents of bronchiolitis and pneumonia, components of the paediatric combined vaccine should include at least respiratory syncytial virus, and possibly also other respiratory viruses like parainfluenza and adenoviruses . The third group of diseases to be considered from the preventive point of view are congenital infections, and vaccines against herpes simplex viruses, cytomegalovirus, or group B streptococci might be included in a combined vaccine to be administered to adolescents in order to afford protection to their future children.

Behring Inst Mitt, 1994 Dec, (95), 1 - 6
Research priorities for vaccines to be used at a global level; Lambert PH; At a global level, there is an urgent need for vaccines against major diseases which are not yet vaccine-preventable . This particularly includes bacterial and viral diarrhoeal diseases, acute respiratory infections, AIDS, malaria, schistosomiasis and meningococcal meningitis . There is also a need for more efficient vaccines against tuberculosis, for a new measles vaccine effective in the young child in the presence of residual maternal antibodies . Therefore, research aiming to define new ways to selectively induce protective responses which would fulfill the needs of immunization programmes, not only in terms of efficacy but also in terms of practicality, represents a real priority . Along this line, modern immunology should be a significant source of new tools to achieve the goal of developing a series of new vaccines which may potentially help to prevent millions of child deaths.

Microb Pathog, 1994 Dec, 17(6), 425 - 30
Comparison of the class-1 outer membrane protein from B:15:P1.16 Neisseria meningitidis strains isolated from patients previously immunized with a serogroup B outer membrane protein vaccine in Norway; Brooks JL et al.; A previous report of a large, double blind, efficacy trial of an experimental Group B meningococcal outer membrane protein vaccine carried out in Norwegian Teenagers, showed a protection rate of 57% . Previous studies had demonstrated the occurrence of mutations in the class-1 outer membrane protein which alter its immunological properties . The occurrence of new mutations might compromise the efficacy of a vaccine and explain the occurrence of any vaccine failures . The porA gene, which encodes expression of the class 1 protein, was sequenced in all isolates from vaccine failures and compared to that of the vaccinating strain H44/76 (B:15:P1.7,16) . The porA DNA and deduced amino acid sequences were all identical to that of the vaccinating strain except for that of one isolate which had a sequence identical to strains previously reported in Norway and England with a 'masked P1.7' epitope . The absence of new mutations in the trial was encouraging for the further development of outer membrane protein vaccines.

Microb Pathog, 1994 Dec, 17(6), 395 - 408
Molecular characterization of the structural gene for the lactoferrin receptor of the meningococcal strain H44/76; Pettersson A et al.; The meningococcal lactoferrin receptor is a promising vaccine candidate since it seems to be antigenically rather stable . Monoclonal antibodies against this protein reacted with more than 50% of the strains tested . To gain further insight in its variability, the IbpA gene from strain H44/76, encoding this protein, was cloned and sequenced . This strain does not cross-react with monoclonal antibodies that recognize LbpA of strain BNCV . The deduced amino acid sequence was found to be 95% homologous to the previously established sequence of LbpA of strain BNCV . A topology model was proposed for LbpA, making use of the sequence comparisons and some general rules for the folding of outer membrane proteins . The protein is supposed to traverse the membrane 26 times in a beta-sheet conformation . The epitope recognized by the monoclonals was mapped and found to reside in the largest predicted surface-exposed loop . No iron-regulation of LbpA expression was found in E . coli, probably because IbpA is located in an operon, the promoter of which was not cloned . Upstream of IbpA, a part of an open reading frame was found . Whereas the LbpA protein shows homology to the transferrin-binding protein 1 (Tbp1), the putative protein encoded by the open reading frame upstream of IbpA shows extensive homology to Tbp2, suggesting that iron-acquisition from lactoferrin, like from transferrin, requires two specific proteins in the outer membrane . The upstream open reading frame is tentatively designated IbpB.

Ugeskr Laeger, 1994 Nov 21, 156(47), 7049 - 57
{Purulent meningitis at the Marselisborg Hospital 1980-1990}; Hansen B et al.; From 1980-1990 245 immunocompetent patients were admitted to The Department of Infectious Diseases, Marselisborg Hospital with purulent meningitis or meningococcal septicaemia . The clinical diagnosis was established by clinical examination and by neutrophil pleocytosis . The aetiological diagnosis was established by demonstration of bacteria in the cerebrospinal fluid by microscopy or culture and by blood culture . Clinical signs of disseminated intravascular coagulation (DIC) or demonstration of meningococcal antibodies (MAT) in serum were considered diagnostic for meningococcal disease . The group comprised 120 males and 125 females aged 0-90 years . One hundred and eleven (45%) had meningococcal disease, 69 (28%) had pneumococcal meningitis, and 20 (8%) had H . influenzae-meningitis . Other aetiologies occurred in one to six cases . No aetiology could be established in 25 (10%) patients . Patients with meningococcal and pneumococcal disease were treated with monotherapy with high doses of penicillin, and H . influenzae-meningitis was treated with ampicillin . In patients with meningitis of unknown aetiology penicillin was used, except in children below the age of five where ampicillin was used . In patients with meningococcal disease the mortality was 5.4%, and 17% developed sequelae . In pneumococcal meningitis the corresponding figures were 13% and 17%, and in H . influenzae-meningitis 0% and 5% respectively . Among 20 patients with other aetiologies one patient (5%) died, and eight (40%) developed sequelae, whereas one patient (4%) died, and one (4%) developed sequelae in the group with meningitis of unknown aetiology . No ampicillin-resistant H . influenzae-strains were demonstrated . We suggest that monotherapy with betalactam-antibiotics is still a valuable treatment for meningitis in Denmark.

Clin Diagn Lab Immunol, 1994 Nov, 1(6), 729 - 36
Development, characterization, and biological properties of meningococcal immunotype L3,7,(8),9-specific monoclonal antibodies; Verheul AF et al.; In this study, we characterize the properties of nine monoclonal antibodies (MAbs) that recognize meningococcal lipopolysaccharides (LPS) . The following three specific MAbs that had not been described previously were elicited in BALB/c mice by using an immunotype L3,7,9 oligosaccharide-tetanus toxoid conjugate in combination with Quil A: 4D1-B3, 3A12-E1, and 4A8-B2 . These MAbs reacted with L3,7,9 LPS on immunoblots and in the LPS enzyme-linked immunosorbent assay (ELISA) and recognised strains containing L3, L3,7, L8 (except 3A12-E1), or L9 LPS in the whole-cell ELISA . The six other MAbs have been described in previous studies (K . Saukkonen, M . Leinonen, H . Abdillahi, and J.T . Poolman, Vaccine 7:325-328, 1989; R.J.P.M . Scholten, B . Kuipers, H.A . Valkenburg, J . Danjert, W.D . Zollinger, and J.T . Poolman, J . Med . Microbiol., in press) and were obtained after immunization with outer membrane protein complexes containing LPS: MN15A11, MN15A8-1, MN15A17-1, MN11A11G, MN14F20-11, and MN14F21-11 . MN15A11 was specific for L3,7,9 LPS and displayed properties similar to those of 3A12-E1 . MN15A17-1, MN14F20-1, and MN11A11G were cross-reactive, and MN14F21-11 was specific for the L1,8 immunotype . Epitope specificities of MAbs reacting with L3,7,(8),9 strains were analyzed . MAbs 4D1-B3, 3A12-E1, and 4A8-B2 recognized phosphoethanolamine group-containing oligosaccharide-specific epitopes . MN15A11 and MN15A17-1 were probably directed against a conformational epitope, although for MN5A11 recognition of an unknown L3,7,9-specific epitope in the 2-keto-3-deoxyoctulosonic acid (KDO)-lipid A region cannot be excluded . MN15A8-1, a strongly cross-reactive MAb, recognized a determinant which included the KDO-lipid A region and the more terminal saccharides.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis Rheum, 1994 Nov, 37(11), 1704 - 6
Deficiency of the beta subunit of the eighth component of complement presenting as arthritis and exanthem; Wulffraat NM et al.; A 13-year-old boy presented with juvenile chronic arthritis of 6 months' duration . Antinuclear antibodies, anti-double-stranded DNA antibodies, and rheumatoid factor were not detected . Western blotting showed a deficiency of the beta subunit of the eighth component of complement . The same deficiency was present in the patient's sister . C8 beta deficiency is usually detected in individuals who survive meningococcal disease . There was no such history in this family . Juvenile chronic arthritis has not previously been described in patients with C8 beta deficiency.

J Med Microbiol, 1994 Nov, 41(5), 339 - 42
Pharyngeal carriage of Neisseria meningitidis before and after treatment of meningococcal disease; Weis N et al.; The aim of the study was to determine whether patients with meningococcal disease carry meningococci in the throat both before and after treatment for the disease . During the 7 months of the study 106 patients with confirmed meningococcal disease were admitted to Danish hospitals, of whom 77 (73%) had a throat swab examined at least once and were included in the study . Sixty-two patients were examined on admission and 52 were examined on discharge; 37 were examined on both occasions . On admission, meningococci were isolated from 18 (49%) of 37 throat specimens examined selectively for pathogenic Neisseria spp . Meningococci were not isolated from any throat specimen taken on discharge from hospital; 47 (90%) of 52 of these specimens had been examined adequately . From an observed carriage rate of 0 out of 47 it can be judged that the carrier rate does not exceed 6.4% (95% confidence limit) . From these results we conclude that it is unlikely that patients who have been treated for meningococcal disease according to the regimens used in Denmark can be the source of infection for secondary cases.

J Infect Dis, 1994 Nov, 170(5), 1224 - 8
Circulating leukemia inhibitory factor levels correlate with disease severity in meningococcemia; Waring PM et al.; Circulating concentrations of the proinflammatory cytokine leukemia inhibitory factor (LIF) were prospectively determined by radioreceptor competition assay (sensitivity, 1 ng/mL) in 33 subjects with meningococcemia . LIF was detected in the plasma of 13 subjects and was associated with development of septic shock (P < .01), disseminated intravascular coagulation (P < .05), multiorgan failure (P < .05), and death (P < .01) . Plasma LIF concentrations were highest (1-1772 ng/mL) at hospital admission and became undetectable within 36 h, and the peak levels correlated inversely with systolic blood pressure (r, -.70, P < .001), peripheral blood leukocyte count (r, -.58, P < .01), and prodromal interval (r, -.60, P < .001) . Plasma LIF concentrations > 400 ng/mL were present only in subjects with fatal fulminant infection . LIF concentrations in plasma collected within 12 h of hospital admission correlated with disease severity in patients with meningococcemia . It is likely that LIF participates in the host response to infection, and it may contribute to the pathogenesis of septic shock.

J Infect, 1994 Nov, 29(3), 289 - 94
Meningococcal meningitis with 'normal' cerebrospinal fluid; Coll MT et al.; A prospective study was made of all patients with normal CSF counts and positive cultures for Neisseria meningitidis diagnosed in "El Valles" County, Barcelona between January 1987 and December 1990 . Meningococcal meningitis was documented in 82 patients, eight of whom (seven children, five boys and two girls with a mean age of 5.6 +/- 3.3 years, and a 69-year-old male patient) had no apparent CSF abnormalities in the initial lumbar puncture . At the time of admission all patients had fever (mean 39.1 degrees C) of 10.8 +/- 5.6 hour duration and petechial rash which had been present for a mean of 3.6 +/- 3.3 hours . Signs of meningeal irritation were not found . A 4-month-old infant with symptoms of circulatory collapse, intracranial hypertension and impairment of consciousness subsequently died of septicemia in 48 hours . Group B N . meningitidis was isolated in six cases (reduced penicillin-susceptibility in two cases) and group C N . meningitidis in the remaining two (reduced penicillin-susceptibility in one case) . Patients without pleocytosis did not differ in a statistically significant fashion from the patients with high pleocytosis in the duration of temperature, and petechial rash, leukopenia, positive blood culture and fatal outcome.

FEMS Immunol Med Microbiol, 1994 Nov, 10(1), 25 - 30
Evidence for the role of glycoprotein G of respiratory syncytial virus in binding of Neisseria meningitidis to HEp-2 cells; Raza MW et al.; Viral glycoproteins G and F are expressed on the surface of cells infected with respiratory syncytial virus (RSV) . We investigated the role of these proteins in the previously reported enhanced binding of Neisseria meningitidis to RSV-infected HEp-2 cells . Virus particles attached to bacteria were detected by immunofluorescence with flow cytometry . Binding of FITC-labelled bacteria to RSV-infected cells was significantly inhibited by monoclonal antibody against glycoprotein G . Unlabelled bacteria interfered with binding of the anti-G monoclonal antibody to these cells . These interactions were not found with a monoclonal antibody against glycoprotein F . We propose that glycoprotein G of RSV expressed on the surface of infected cells might act as an additional receptor for meningococci.

Eur J Pediatr, 1994 Nov, 153(11), 821 - 4
Mortality from group C meningococcal disease: a case for a conjugate vaccine?
Riordan FA, Marzouk O, Thomson AP, Sills JA, Hart CA.
This 17-year retrospective review of children with meningococcal disease (MCD) has determined the mortality due to serogroup C, in order to assess the potential impact of a group C conjugate vaccine . Four hundred and forty-nine cases of MCD were admitted to our hospitals during 1977-1993; 78 due to group C, 11 of whom died . There was a significant increase in the proportion of cases due to group C from 1986 onwards (10% vs 21%), and an increase in the total number of cases of MCD (151 vs 298) . The currently available group C polysaccharide vaccine has low efficacy below 2 years of age and could not have prevented 54 cases of group C disease . A conjugate group C vaccine administered between 2 and 4 months of age could have prevented 68 cases, including all fatal cases . The recent increase in MCD is partly due to an increase in group C disease . A meningococcal group C conjugate vaccine could prevent most cases of infection due to group C, and decrease the mortality from MCD by up to 30%.

Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi, 1994 Nov-Dec, 35(6), 542 - 5
Neonatal meningococcal meningitis: report of two cases; Chiu CH et al.; Two neonates with meningococcal meningitis and meningococcemia are reported . The two, aged 28 and 16 days, respectively, presented similar symptoms of fever, poor appetite and poor activity . Both blood and cerebrospinal fluid cultures of each patient grew Neisseria meningitidis . The isolated bacteria were sensitive to penicillin, and both patients recovered completely after penicillin treatment for 22 and 15 days, respectively . In the antibiotic era, only 22 cases of neonatal meningococcal meningitis have been reported in the English literature . Among these reports, at least 7 patients survived without sequelae; 6 of those were treated with different combinations of antibiotics, including penicillin, for variable durations of 7-14 days . Therefore, effective antibiotic therapy for 14 days should be adequate in the treatment of uncomplicated neonatal meningococcal meningitis and meningococcemia.

Microbiology, 1994 Nov, 140 ( Pt 11), 2951 - 60
Immunization with a multiple antigen peptide containing defined B- and T-cell epitopes: production of bactericidal antibodies against group B Neisseria meningitidis; Christodoulides M et al.; Previous analysis of the class 1 outer-membrane (OM) protein of Neisseria meningitidis has identified discrete epitopes to be potential targets for immune attack . The conformation of these epitopes is important for inducing antibodies which can react with the native protein and promote complement-mediated lysis of the meningococcus . The multiple antigen peptide (MAP) system, which consists of an oligomeric branching lysine core to which are attached dendritic arms of defined peptide antigens, confers some conformational stability and also allows for the preparation of immunogens containing both B-cell and T helper (Th)-cell epitopes . In this study, MAPs were synthesized to contain (i) the subtype P1.16b meningococcal class 1 protein B-cell epitope (B-MAP), and (ii) the P1.16b epitope in tandem with a defined Th-cell epitope, chosen from tetanus toxin (BT-MAP) . The B-MAP was nonimmunogenic in animals . In contrast, incorporation of the Th-cell epitope into BT-MAP induced a strong humoral response towards the class 1 protein B-cell epitope . Antisera from immunized mice and rabbits reacted in ELISA with synthetic peptides containing the B-cell epitope, and also cross-reacted with meningococcal OMs from strains of subtype P1.16b and P1.16a . Murine and rabbit antisera showed similar reactivity and epitope specificity, but did not react with denatured class 1 protein in Western blotting, indicating the predominance of antibodies directed towards conformational epitopes . The antisera from rabbits immunized with BT-MAP promoted complement-mediated bactericidal killing not only of the homologous meningococcal subtype P1.16b strain but also of subtype P1.16a.

Infect Immun, 1994 Nov, 62(11), 4874 - 80
Low levels of vitronectin and clusterin in acute meningococcal disease are closely associated with formation of the terminal-complement complex and the vitronectin-thrombin-antithrombin complex; Hogasen K et al.; Patients with terminal complement deficiencies and thus impaired lytic efficiency have a highly increased likelihood of contracting invasive meningococcal infections but generally experience a mild disease course . Deficiencies of lysis inhibitors might therefore be associated with severe disease . We have quantified the complement lysis inhibitors vitronectin and clusterin, as well as complexes containing the proteins, in plasma from patients with acute meningococcal disease . At hospital admission, the median vitronectin concentrations were 0.10 (range, 0.04 to 0.17) g/liter in 10 septic patients and 0.19 (0.09 to 0.47) g/liter in 14 nonseptic patients (P = 0.001) . The corresponding clusterin concentrations were 0.09 (0.01 to 0.13) and 0.14 (0.06 to 0.29) g/liter (P = 0.005) . The vitronectin-thrombin-antithrombin complex concentration was 1.8 (0.22 to 35.6) arbitrary units (AU)/ml in septic patients, but the complex was not detectable in most nonseptic patients (< 0.10 to 0.16 AU/ml) (P < 0.0001) . The corresponding levels of the terminal complement complex (contains vitronectin and clusterin) were 4.4 (3.6 to 20.1) and 2.6 (1.6 to 4.7) AU/ml (P = 0.0005) . We found no evidence of constitutively low levels of vitronectin or clusterin in patients contracting meningococcal disease . The low levels of the proteins may partly be explained by hemodilution, extravasation, and increased consumption due to incorporation into complexes which are quickly removed from circulation.

Rev Prat, 1994 Oct 15, 44(16), 2172 - 6
{Acute viral meningitis}; Choutet P et al.; Viral meningitis are the most frequent cause of clear cerebrospinal fluid (CSF) meningitis and are usually benign . The viral nature is suggested by clinical arguments (context, associated manifestations) and particularly the analysis of CSF, typically lymphocytic . However, problems of CSF interpretation may occur during the polymorphonuclear reaction at the beginning of such meningitis and after elevated protein or low glucose concentration . The main differential diagnosis are: partially treated bacterial meningitis, the beginning of meningococcal meningitis, listeriosis or tuberculous meningitis which need and urgent and specific treatment . The most common agents are the enteroviruses . The etiology can only be detected through careful virological investigations . These studies may be useful in outbreaks or in epidemiological studies.

N Z Med J, 1994 Oct 12, 107(987), 399 - 402
Meningococcal disease in New Zealand: an audit of disease notification and contact management; Bandaranayake D; AIMS . To determine variations in practice across New Zealand for the notification and contact management of meningococcal disease and recommend action . METHODS . A retrospective survey using a questionnaire conducted during August and September 1992 . The disease notification component of the audit looked only at process (post notification) rather than completeness of notification . RESULTS . The results indicated that there was considerable variation in practice across the country . Concerns expressed by respondents related to the availability of and payment for prescribed prophylactic antibiotics, contact definition, protocol availability and the appropriate delegation of duties . Deficiencies were identified in the above areas of concern as well as in follow-up procedures for contacts, record keeping and communication . CONCLUSIONS . Major variations in practice across the country which may be counterproductive to outbreak control should be minimised . A minority of area health boards (AHBs) and districts have well developed protocols that could be the basis for developing standards of good practice for the whole country.

J R Army Med Corps, 1994 Oct, 140(3), 155 - 8
An outbreak of cerebrospinal fever in a 19th century British Mediterranean naval base; Savona-Ventura C; Epidemic Meningococcal meningitis first made its definite appearance in Europe in the beginning of the nineteenth century . The first recorded epidemic in the Maltese Islands, which straddled the sea-routes of the Mediterranean, occurred in the late nineteenth century . This paper describes a manuscript report prepared at the request of the Lieutenant Governor regarding this epidemic in the light of the contemporary knowledge about the infection.

Burns, 1994 Oct, 20(5), 471 - 2
Skin and extremity loss in meningococcal septicaemia treated in a burn unit; Harris NJ et al.; Meningococcal septicaemia is a severe systemic illness which has an overall mortality of 15 per cent . It differs from meningococcal meningitis in clinical presentation, treatment, complications and prognosis . Skin and extremity loss are particular problems seen in meningococcal septicaemia . As critical care improves more patients are being seen with these complications . We report two patients in which these complications are demonstrated . Both patients underwent multiple autogenic and allogenic skin grafting procedures for skin loss . Apparently necrotic extremities were initially treated conservatively, with good results . The total area of necrotic tissue reduced dramatically with this treatment . Despite this, however, one patient required a Syme amputation, in the other, two toes on the affected foot separated painlessly at the metatarsophalangeal joint . We also discuss some of the pathophysiology behind skin necrosis . A popular view at present is that endotoxin from the cell wall of Neisseria meningiditis initiates the release of vasoactive cytokines by the host . High levels of interleukin-1 and interleukin-6 have been associated with a greater likelihood of fatality.

J Infect Dis, 1994 Oct, 170(4), 848 - 53
Fc gamma receptor IIa (CD32) polymorphism in fulminant meningococcal septic shock in children; Bredius RG et al.; Antibodies are essential in host defense against Neisseria meningitidis . Therefore, interactions among IgG and Fc receptors (Fc gamma R) on phagocytes may be crucial . Genetic polymorphic forms of Fc gamma RIIa (CD32) express different functional activities . In a retrospective study, Fc gamma R polymorphisms were determined in 25 children who survived fulminant meningococcal septic shock: 11 had Fc gamma RIIa-R/R131, the poor IgG2-binding allotype, which is a significantly more frequent rate than found in a healthy white population (44% vs . 23%; P = .028; odds ratio = 2.67; 95% confidence interval, 1.09-6.53) . The relevance of this finding was further supported by the fact that neutrophils with the Fc gamma RIIa-R/R131 allotype phagocytized N . meningitidis opsonized with polyclonal IgG2 antibodies less effectively than did IIa-H/H131 neutrophils . Our findings suggest an important role for anti-N . meningitidis IgG2 and the Fc gamma RIIa polymorphism in host defense against systemic meningococcal infections.

Infect Immun, 1994 Oct, 62(10), 4419 - 24
Immune response of Brazilian children to a Neisseria meningitidis serogroup B outer membrane protein vaccine: comparison with efficacy; Milagres LG et al.; Since 1986, serogroup B Neisseria meningitidis has caused approximately 80% of the meningococcal disease in Brazil . In 1988, an epidemic caused by N . meningitidis B:4:P1.15 was recognized in the greater Sao Paulo area of Brazil . The Sao Paulo state government decided to vaccinate children from 3 to 83 months of age with a vaccine consisting of serotype 4 outer membrane protein and group C meningococcal polysaccharide that was produced in Cuba . About 2.7 million children were vaccinated during two immunization campaigns conducted in 1989 and 1990 . Because of this, a case-control study was designed to determine vaccine efficacy against group B meningococcal disease . The purpose of our study was to compare the antibody response with the protection from disease estimated from the case-control study . We measured the immune responses of vaccinees by enzyme-linked immunosorbent assay (ELISA), immunoblot, and bactericidal assay . The development of bactericidal antibodies was age dependent and in good agreement with the results of the case-control study . Only 40% of vaccinees showed fourfold or greater increases in bactericidal antibody titers after vaccination . A poor correlation between antibody levels detected by ELISA and those by bactericidal assay was found . Immunoblot analysis showed that about 50% of the serum samples with bactericidal titers higher than 1:4 were reactive with class 1 outer membrane protein . We conclude that the bactericidal assay is a good, laboratory-based, functional assay for the study of vaccine immunogenicity and that an effective solution to group B meningococcal disease remains to be demonstrated.

Epidemiol Infect, 1994 Oct, 113(2), 267 - 74
Sero/subtyping of Neisseria meningitidis isolated from patients in Spain; Vazquez JA et al.; To know the types of meningococcal strains in Spain, we serotyped and subtyped 743 Neisseria meningitidis isolates recovered between 1990 and 1992 from patients . A great number of serogroup B, serogroup C and non-groupable meningococci reacted with the serotyping reagents while many serogroup C and non-groupable isolates did not react with the serosubtyping reagents (78.2% and 54.8% respectively); only 8.9% of serogroup B meningococci were non-subtypeable (NST) . Distribution of serotypes was similar in serogroup C and in non-groupable strains . Isolates showed great variability in antigenic phenotypes (71 in serogroup B, 20 in serogroup C and 25 in non-groupable meningococci) . The most frequent antigenic combinations were 4:P1.15 (39.8%) in serogroup B, 2b:NST (55.8%) in serogroup C and 2b:NST (35.6%) in non-groupable meningococci.

FEMS Immunol Med Microbiol, 1994 Oct, 9(4), 299 - 305
Reliability of laboratory models in the analysis of TBP2 and other meningococcal antigens; Ferron L et al.; The lack of experimental models suitable for the study of meningococcal pathogenicity led us to investigate if those actually in use (culture in iron-restricted media and animal models) provide results comparable with the responses observed in vivo during infection . In this work we studied three invasive strains cultured both in laboratory media and in human plasma, analysing the immune responses elicited in mice against membrane antigens and comparing them with those seen using homologous human convalescent sera . Outer membrane protein profiles observed after culture in plasma were different and more complex than those obtained after growth in laboratory media . Analogous differences were observed in the antigenic profiles, detecting some antigens recognized by human, but not mouse sera, and vice versa . However, the response to one of the major iron-regulated outer membrane antigens, the transferrin binding protein 2 (TBP2), was unaffected by the culture medium or the model, human or mouse, used for the analysis . In conclusion, we have found that results of antigenic analysis change depending on the culture conditions and animal models used . For the meningococcal antigen TBP2, growth in iron-restricted laboratory media and a mouse model provide results which correlate well with those observed using convalescent human serum from individuals recovered from infections . We suggest that careful analysis and evaluation of experimental results and their comparison with in vivo elicited immune responses are essential in order to get accurate extrapolations for experimental vaccine designs.

Pediatr Infect Dis J, 1994 Oct, 13(10), 867 - 73
The role of heparin in the prevention of extremity and digit necrosis in meningococcal purpura fulminans; Kuppermann N et al.; In order to gather data regarding the utility of heparin therapy in limiting digit and extremity necrosis resulting from meningococcal purpura fulminans in children, we reviewed the charts of 24 pediatric patients with PF associated with meningococcal disease . Our study population was comprised of the 13 patients who survived more than 2 days . Clinical and outcome data were compared between the group of patients who received therapeutic heparin treatment in the initial 72 hours (> or = 50 units/kg bolus followed by an infusion, three patients) and the group who did not (10 patients) . Demographic and initial clinical and laboratory findings were similar between groups (P > 0.15) . When the two groups were compared for dermatologic and orthopedic sequelae, the mean number of digits (6.3 vs . 11.1; P = 0.35) and extremities (1.7 vs . 3.0; P = 0.17) with necrosis was less in those patients who received therapeutic doses of heparin, although the differences were not statistically significant . When only those patients on whom diffuse purpura were noted on admission were compared, these differences were greater . This small, retrospective series suggests that heparin therapy may limit digit and extremity necrosis when used early and in therapeutic doses in meningococcal purpura fulminans . Therefore, a larger, prospective controlled trial is warranted.

Arch Pediatr, 1994 Oct, 1(10), 908 - 12
{Homozygote CB deficiency revealed by recurrent Neisseria meningitidis infections in an adolescent}; Louaib D et al.; BACKGROUND--Meningococcal infections associated with late complement component deficiency are rarely severe and usually occur during adolescence and adulthood . We report severe manifestations in a boy in whom the first episode appeared early . CASE REPORT--A 14 year-old gypsy boy was admitted because of a febrile meningococcal meningitis that was complicated by a rapidly extensive and necrotic purpura, obnubilation and clotting abnormalities without hemodynamic anomalies . The patient was given symptomatic therapy and a 12-day course of antibiotics that resulted in rapid and complete recovery . Medical history of this patient showed that he had been admitted at the age of 3 years for a severe febrile purpura with septic shock and clotting abnormalities followed by rapid and complete recovery after symptomatic and antibiotic therapy . No germ had been then isolated . The complement system was studied 3 weeks after the second hospitalization: total hemolytic complement activity could not be detected and C2, C3 and C4 were normal . Examination of the terminal pathway-revealed total C8 deficiency . The patient received meningococcal vaccine and was discharged on oral penicillin prophylaxis . He remained healthy during the ensuing 4 years . CONCLUSIONS--Meningococcal infections associated with late complement component deficiency are generally uncomplicated but they remain potentially severe . Early screening for this late complement component deficiency should be considered after severe clinical manifestations.

Clin Microbiol Rev, 1994 Oct, 7(4), 559 - 75
Current status of meningococcal group B vaccine candidates: capsular or noncapsular?
Diaz Romero J, Outschoorn IM.
Meningococcal meningitis is a severe, life-threatening infection for which no adequate vaccine exists . Current vaccines, based on the group-specific capsular polysaccharides, provide short-term protection in adults against serogroups A and C but are ineffective in infants and do not induce protection against group B strains, the predominant cause of infection in western countries, because the purified serogroup B polysaccharide fails to elicit human bactericidal antibodies . Because of the poor immunogenicity of group B capsular polysaccharide, different noncapsular antigens have been considered for inclusion in a vaccine against this serogroup: outer membrane proteins, lipooligosaccharides, iron-regulated proteins, Lip, pili, CtrA, and the immunoglobulin A proteases . Alternatively, attempts to increase the immunogenicity of the capsular polysaccharide have been made by using noncovalent complexes with outer membrane proteins, chemical modifications, and structural analogs . Here, we review the strategies employed for the development of a vaccine for Neisseria meningitidis serogroup B; the difficulties associated with the different approaches are discussed.

Mol Microbiol, 1994 Oct, 14(1), 141 - 9
Molecular analysis of the biosynthesis pathway of the alpha-2,8 polysialic acid capsule by Neisseria meningitidis serogroup B; Edwards U et al.; The genes encoding all enzymes necessary for capsular polysaccharide biosynthesis in Neisseria meningitidis B are located on a 5 kb DNA fragment within the chromosomal cps gene cluster . Nucleotide sequence analysis revealed four open reading frames (ORFs), which can encode proteins with molecular masses of 41.4 kDa, 24.9 kDa, 38.3 kDa, and 54.4 kDa, respectively . These ORFs constitute a transcriptional unit as demonstrated by Northern blots . Primer extension analysis revealed that the transcriptional start site is preceded by a nucleotide sequence with homologies to the sigma 70 consensus promoter sequence of Escherichia coli . Functional analysis of the proteins encoded by the ORFs indicated that ORF2 encodes the CMP-NeuNAc synthetase, ORF3 encodes the NeuNAc condensing enzyme, and ORF4 encodes the alpha-2,8 polysialyltransferase . ORF1 encodes an enzyme, which provides a precursor molecule for synthesis of monomeric NeuNAc . In E . coli the subcloned ORFs 2-4 were able to synthesize a high-molecular-weight alpha-2,8 polysialic acid . In contrast, inactivation of ORF1 in the meningococcal genome resulted in a complete loss of capsule production . A regulatory enzyme, the CMP-NeuNAc hydrolase, which cleaves CMP-NeuNAc to CMP and NeuNAc, was not found as a part of the capsular polysaccharide biosynthesis gene operon or within the cps gene cluster.

Ann Gastroenterol Hepatol (Paris), 1994 Oct, 30(5), 227 - 31
{Current status of immunization in the Armed Forces: need of continuous adaptation of vaccinations against cerebrospinal meningitis, typhoid and hepatitis A}; Meyran M et al.; The history of military medicine has always been closely linked with that of vaccinations . Doctors of Armed Forces, doctors of collectivities, have contributed to vaccination progresses in large amounts . But evolutions are often rapid here: epidemiological modifications, improvements in the existing vaccines or creation of new vaccines, diversification of military specificities . Three recent modifications in the vaccination schedule of the Armed Forces show this necessary adaptation: systematization of the meningococcal A+C vaccination during the incorporation, because of the modification of the disease's epidemiological profile; increase of the frequency in serogroup C with a mortality increase (9 cases of death out of 10 observed between 1991 and 1992); cancellation of antityphoid vaccination for recruits serving in home country . Indeed the disease has become rare in France, and this is often due to imported cases (3 cases in the Armed Forces in 1992); introduction in 1994 of vaccination against viral hepatitis A, systematic under the age of 25 years and after a serological selection above for servicemen having to serve overseas or for outside operations . These 3 examples show the necessity to have updated and adaptable vaccination schedules.

Lett Appl Microbiol, 1994 Oct, 19(4), 232 - 6
Rapid identification of pathogenic neisserias using the Identicult-Neisseria test; Moyes A et al.; A rapid enzymatic method using chromogenic substrates for the rapid identification of pathogenic neisseria (Identicult-Neisseria, Scott Laboratories Inc., CA, USA) was tested in parallel with the rapid carbohydrate utilization test (RCUT) and the Phadebact Monoclonal GC Test against 198 consecutive clinical isolates of oxidase-positive Gram-negative diplococci (118 Neisseria gonorrhoeae, 76 N . meningitidis and four N . lactamica) . On initial testing the Identicult-Neisseria gave a 95% overall concordance (97.5% N . gonorrhoeae, 90.8% N . meningitidis) with the RCUT and Phadebact tests; the corresponding figures after repeat testing were 98% overall concordance (98.3% N . gonorrhoeae, 97.4% N . meningitidis) . Two of the three strains of N . gonorrhoeae mis-identified as N . meningitidis on primary testing were also mis-identified on repeat testing . Seven strains of N . meningitidis were mis-identified on initial testing (six as Moraxella catarrhalis and one as N . lactamica) and two on repeat testing (both as Mor . catarrhalis) . We conclude that the Identicult-Neisseria is not sufficiently reliable for the culture confirmation of gonococci and meningococci.

Microb Pathog, 1994 Oct, 17(4), 227 - 37
Insertional inactivation of the gene for the meningococcal lactoferrin binding protein; Quinn ML et al.; The lactoferrin binding protein (LBP) of Neisseria meningitidis (the putative meningococcal receptor for human lactoferrin, LF), has been previously characterized as an outer-membrane protein of approximately 105 kDa . Using N-terminal amino acid sequence to generate an oligonucleotide probe, a clone from a lambda gt11 phage library was isolated . This clone was subjected to shuttle mutagenesis, in which an erythromycin mini-transposon was used to interrupt the LBP coding sequence . This insertion mutation was introduced into the meningococcus . A N . meningitidis strain that carried this transposon insertion no longer produced the 105 kDa protein . The absence of this protein was correlated with the inability to bind LF or to use LF as an iron source . The LBP mutant was able to grow with other Fe sources and demonstrated no other visible membrane protein alterations . These data confirm the suggestion that LBP is the meningococcal receptor.

Mol Microbiol, 1994 Oct, 14(1), 173 - 84
Distinct mechanisms of interactions of Opc-expressing meningococci at apical and basolateral surfaces of human endothelial cells; the role of integrins in apical interactions; Virji M et al.; Interactions of Opc-expressing Neisseria meningitidis with polarized and non-polarized human umbilical vein endothelial cells (Huvecs) were investigated . Metabolic inhibitors and cytochalasin D treatment showed that host cellular and cytoskeletal functions were important for Opc-expressing bacterial association with Huvecs at the apical surface . In addition, this interaction required the presence of serum in the incubation medium whilst association with non-polarized cells did not require serum . Pre-exposure of Opc-expressing bacteria to serum was sufficient to increase the number of bacterial interactions at the apical surface; B306, a monoclonal antibody (mAb) against Opc, inhibited these interactions, suggesting that Opc binds to serum factor(s) and this in turn increases adherence to Huvecs . The receptors involved in this 'sandwich' adherence belong to the integrin family since the interaction was inhibited by peptides containing the amino acid sequence arginine-glycine-aspartic acid (RGD) and the tetrapeptide RGDS (but not the peptide RGES) was inhibitory . Non-polarized cells appeared to expose receptors/sites that bound to Opc-expressing bacteria directly, did not require serum factors and were not inhibited by RGD-containing peptides . Serum-dependent interactions of Opc-expressing bacteria to apical surface was inhibited significantly by several mAbs against alpha v beta 3 integrins . Some mAbs against alpha 5 and beta 1 caused partial inhibition; antibodies that did not block the function of beta 1 integrins or the mAbs against alpha 2 integrins were not inhibitory to bacterial interactions with Huvecs . Purified vitronectin supported adherence of Opc-expressing bacteria to Huvecs but not of Opc- bacteria . These interactions were inhibited by mAb B306 against Opc, by RGDS peptides as well as by blocking antibodies directed against alpha v beta 3 but not antibodies against other integrins . These data suggest that a sequence of molecular events resulting in trimolecular complexes at the endothelial surface may drive neisserial invasion of Huvecs . The expression of Opc appears to enable bacteria to utilize the normal signal-transduction mechanism of host cells via ligands in sera that adhere to endothelial cell integrins.

J Med Microbiol, 1994 Oct, 41(4), 236 - 43
Lipo-oligosaccharide immunotyping of Neisseria meningitidis by a whole-cell ELISA with monoclonal antibodies; Scholten RJ et al.; To assess the applicability of a whole-cell ELISA (WCE) with monoclonal antibodies (MAbs) for lipo-oligosaccharide (LOS) immunotyping of Neisseria meningitidis, 675 meningococcal isolates obtained in 1989 and 1990 in the Netherlands and 57 isolates collected in 1974, of which the immunotype had been determined previously by microprecipitation, were analysed . Despite the lack of specific MAbs for L2 and L4, an algorithm was developed for the assignment of immunotypes on the basis of the reaction patterns of the reference strains and these isolates to a combination of 14 MAbs . The immunotypes found by WCE were in accordance with those obtained by microprecipitation and the results from WCE were reproducible . The distribution of immunotypes among isolates of the various serogroups in the Netherlands in 1989-1990 is presented . Based on the reaction patterns of the isolates, two main categories of related immunotypes could be distinguished among isolates of serogroups B and C: L2/L4 and L3/L1/L8 . Some isolates of the latter category were of one immunotype, but many isolates expressed one or two additional immunotypes, either strongly or weakly, indicating that the differences in this category are quantitative rather than qualitative . The results of this study have demonstrated that the WCE method for LOS immunotyping is easily applicable and provides better definition of test strains for in-vitro bactericidal assays and research into pathogenesis.

Epidemiol Infect, 1994 Oct, 113(2), 275 - 81
Hereditary deficiency of the seventh component of complement and recurrent meningococcal infection: investigations of an Irish family using a novel haemolytic screening assay for complement activity and C7 M/N allotyping; Egan LJ et al.; Terminal complement component deficiency predisposes to meningococcal infection and is inherited in an autosomal co-dominant manner . An Irish family is described, in which 2 of 3 brothers had recurrent meningococcal infection . A novel screening assay was used to investigate for terminal complement deficiency and the 2 affected brothers were found to be completely deficient in the seventh component of complement (C7) . Enzyme-linked immunosorbent assay for C7 revealed lower than normal levels in the remaining brother and parents . C7 M/N protein polymorphism allotyping, used to investigate the segregation of the C7 deficiency genes, showed that the apparently complement sufficient brother was heterozygous C7 deficient and a carrier of one of the deficiency genes . Complement screening should be carried out in any individual suffering recurrent meningococcal infection or infection with an uncommon meningococcal serogroup . Identification of complement deficient patients allows the implementation of strategies to prevent recurrent infection.

Vaccine, 1994 Sep, 12(12), 1064 - 70
Non-specific modulation of the immune response with liposomal meningococcal lipopolysaccharide: role of different cells and cytokines; Petrov AB et al.; The immunomodulating action of Neisseria meningitidis lipopolysaccharide (LPS) incorporated into liposomes and the activation of different populations of immunocompetent cells or the secretion of cytokines were studied . LPS stimulated an anti-sheep red blood cell (SRBC) plaque-forming cell response in the spleen of mice after simultaneous injection of LPS and SRBC but if LPS was administered 3 days before the immunization with SRBC the response to SRBC was strongly suppressed . After the incorporation of LPS into liposomes the stimulation index was increased from 6 to 19 and the liposomal LPS did not suppress the immune response to SRBC . The incorporation of LPS into liposomes leads to enhancement of B-mitogenic properties of LPS, as liposomal LPS stimulated the proliferation of splenocytes in mice better than free LPS and has no influence on the thymocytes . The liposomal LPS induced more prolonged and significant accumulation of IgM-secreting cells in the spleen of mice in comparison with the free LPS . Liposomal LPS also induced more active accumulation of IFN-gamma in human peripheral blood mononuclear cells and less active accumulation of monokines, contributing to the realization of the toxic properties of endotoxin (IL-1 alpha, TNF-alpha, IL-6 and GM-CSF) . These results demonstrated that the incorporation of N . meningitidis LPS into liposomes dramatically changed its immunomodulating activity . The data obtained are important for the construction of an adjuvant formulation for synthetic immunogens capable of inducing genetically unrestricted immune responses.

Kansenshogaku Zasshi, 1994 Sep, 68(9), 1117 - 21
{Purpura fulminans complicating pneumococcal sepsis: a case report}; Ohnishi M et al.; An unusual case of a 67-year-old man is reported with fulminant pneumococcal sepsis . He had been healthy before, and the identified predisposing factors were only that he was a chronic alcohol drinker and was a HCV carrier . He presented signs of acute renal failure, liver dysfunction, adult respiratory distress syndrome and disseminated intravascular coagulation . Subsequently purpura fulminans (symmetrical peripheral gangrene) with major extremity involvement developed . He finally survived with amputation of both legs, right forearm and two fingers of left hand . Purpura fulminans is a rare catastrophic disease, with initial hemorrhagic skin lesions that progress to gangrene . It usually follows an infectious illness, and although it most commonly occurs in children, it can occur in adults with predisposing factors such as alcoholic, asplenia, AIDS and so on . In adults, pneumococcus and meningococcus are microorganisms that have been reported most frequently as caused agents in Europe and America . But in Japan the previously reported adult case was the only one complicating Xanthomonas maltophilia sepsis, and none accompanying pneumococcal sepsis . Congenital protein C deficiency is recognized to be able to cause purpura fulminans especially in patients with risk factors . In our case, protein C antigen was decreased in the acute stage but gradually increased later toward normal, so this decrease was thought to be concomitant with the initial disseminated intravascular coagulation rather than compatible with protein C deficiency.

Clin Exp Rheumatol, 1994 Sep-Oct, 12(5), 531 - 3
Recurrent sterile arthritis following primary septic meningococcal arthritis; Mader R et al.; Primary septic meningococcal arthritis (PSMA) is an unusual manifestation of meningococcal disease . With appropriate antibiotic therapy, complete recovery is the rule . A "postinfectious arthritis" in the previously infected joint may ensue, however . A patient who developed a recurrent sterile arthritis following PSMA, after a symptom-free interval, is described . Possible pathogenetic mechanisms and the clinical implications are discussed.

Pathol Res Pract, 1994 Sep, 190(8), 737 - 49
Cardiomyopathy in childhood and adult life, with emphasis on hypertrophic cardiomyopathy; Landing BH et al.; Over 60 entries in the genetic catalog have cardiomyopathy features--32 autosomal dominant, 35 autosomal recessive and X-linked . Over 40 present in, or can have survival into, adult life . Major clinicopathologic categories of these cardiomyopathic disorders included: sudden death (13 entities); cardiac conduction disturbance important feature; associated myopathy or motor dysfunction; storage diseases with cardiac involvement; cardiac amyloidoses; and, other categories . Genes, abnormality of which can cause hypertrophic cardiomyopathy (HCM), have been identified on chromosomes 1, 14 and 15, the locus on chromosome 14 involving the B-myosin heavy chain gene, but at least one unidentified locus is known to exist and there is a suggestive locus on chromosome 16, so that HCM is not a single disease but a group of disorders with clinicopatholopic similarities . To investigate these aspects of HCM in some detail, sixty-six patients with "sharply demarcated" differential myocardial fiber bundle hypertrophy (DMBH), considered to be of significant degree, from a pediatric autopsy data base of approximately 8,000 cases, were reviewed . Twenty-three of the patients died suddenly, without antecedent significant cardiac dysfunction, seven had clinical congestive heart failure of varying duration, three were stillborn, six showed evidence of aspiration of amniotic sac content (three had history of fetal distress), five had ischemic bowel disease, three (two with clinical cerebral palsy and one with Ondine's curse syndrome) had cerebral atrophy and sclerosis and one had extensive more acute encephalomalacia, and a variety of other major "causes of death" were present . Whether all infants and children with DMBH meeting the criteria used, who do not have congenital heart disease, have dominant hypertrophic cardiomyopathy (HCM) cannot be established by studies of this type, but the "concentration" of a gene or genes for HCM in pediatric autopsy series because the strong effect of HCM on life expectancy is relevant to this possibility . The data raise the question that stillbirth, fetal distress with aspiration of amniotic sac content, ischemic bowel disease and cerebral atrophy and sclerosis may be hitherto underappreciated features of HCM in childhood, and that patients with HCM may be peculiarly liable to die with certain types of septic shock, such as acute meningococcemia . In the material of this study, sudden death was statistically more frequent in females than in males in childhood (p < .029).

J Clin Microbiol, 1994 Sep, 32(9), 2185 - 91
Characterization of strains of Neisseria meningitidis recovered from complement-sufficient and complement-deficient patients in the Western Cape Province, South Africa; Orren A et al.; Complement deficiency has been associated with increased susceptibility to meningococcal disease . In order to determine whether special meningococcal strains caused disease in complement-deficient (CD) patients, 17 Neisseria meningitidis strains recovered from patients in the Western Cape Province, South Africa, known to be CD were compared with 124 routine isolates obtained from patients living in the same area . Serogrouping of the strains from the CD subjects revealed that the common serogroups, particularly serogroup B, predominated . However, the prevalence of rare serogroups among isolates from CD subjects was significantly higher than that found among isolates from the control group . Sero- and subtyping of the class 1 and class 2 or 3 outer membrane proteins showed no significant difference between isolates from CD subjects and the routine clinical isolates . Multilocus enzyme electrophoresis of the 141 isolates revealed six clusters of electrophoretic types (ETs) and two unrelated ETs . The same degree of genetic diversity existed in ETs of isolates from CD subjects and the control group . However, the ET-5 complex, which is known to be associated with epidemic disease, was found in 22 (18%) of the routine clinical isolates but in none of the isolates from the CD subjects . This difference was marginally significant . What was highly significant was the finding that 8 of the 17 isolates from CD subjects were in one ET cluster, cluster F, which comprised a total of 20 isolates . Thus, our results show a difference in the clonal compositions of the strains that infect CD subjects in comparison with the clonal compositions of those that cause clinical infections in the population at large.

J Pediatr Surg, 1994 Sep, 29(9), 1248 - 9
Gastrointestinal mucormycosis causing an acute abdomen in the immunocompromised pediatric patient--three cases; Vadeboncoeur C et al.; Mucormycosis is an infection caused by a ubiquitous fungus in immunocompromised individuals . Typically, it invades blood vessels, producing thrombosis and tissue infarction . This infection spans all pediatric age groups and can lead to hollow viscus perforation and bowel obstruction . A 30-month old male with large cell anaplastic lymphoma had a bowel obstruction . During emergency laparotomy, an ileoileal intussusception was identified, which required resection and anastomosis . In the pathological specimen, fungi of the Mucorales order were found to be associated with tissue necrosis . On the eighth day of life, a premature infant had abdominal distension secondary to bowel perforation . Partial gastric resection and multiple intestinal stomas were performed . Death occurred soon after, secondary to multiorgan failure . The autopsy and surgical specimens showed widespread mucormycosis . An adolescent had meningococcemia-induced septic shock . During recovery, hemorrhagic colitis developed, which led to perforation . The subtotal colectomy specimen showed widespread mucormycosis . The laparotomy findings are typical (black necrotic tissue involving the bowel), and when seen in the immunocompromised patient, should make one suspect gastrointestinal mucormycosis . Aggressive surgical debridement of devitalized tissue augmented by intravenous antifungal medication is the mainstay of treatment.

J Infect, 1994 Sep, 29(2), 211 - 4
Primary meningococcal conjunctivitis and the need for prophylaxis in close contacts; Stansfield RE et al.; We present three cases of primary meningococcal conjunctivitis associated with systemic sepsis . The management of such patients should include combined topical and parenteral therapy with appropriate chemoprophylaxis for close contacts of cases.

Commun Dis Rep CDR Rev, 1994 Aug 19, 4(9), R97 - 100
Meningococcal infections in England and Wales: 1993; Jones DM et al.; One thousand two hundred and ninety-seven meningococcal isolates of clinical significance were submitted for examination to the PHLS Meningococcal Reference Unit in 1993; almost the same total as in 1992 . Changes in the number of isolates from individual regions ranged from falls of 25% to increases of 42% . The incidence of meningococcal disease rose late in 1993, apparently affected by the epidemic of influenza . The number of statutory notifications reported to the Office of Population Censuses and Surveys was--for the first time--markedly higher than the number of laboratory diagnosed cases . Serodiagnosis was used to confirm an increased number of clinically suspected cases in 1993.

Commun Dis Rep CDR Rev, 1994 Aug 19, 4(9), R101 - 4
Epidemiology of meningococcal disease and a community outbreak in Somerset; Gunnell DJ et al.; We describe the epidemiology of meningococcal disease in Somerset and a community outbreak in one district . Fifty-seven cases of meningococcal disease occurred in residents of Somerset between 1 May 1990 and 30 April 1993 (incidence 4.7/100,000/year), of whom six died . Thirteen of the cases occurred in one local authority area in a six month period from 1 November 1992 to 30 April 1993; an incidence of 26.6/100,000/year . Twenty-seven patients were given benzyl-penicillin before admission to hospital . General practitioners were significantly more likely to give benzylpenicillin to patients with rashes . The proportion that received prophylaxis tended to increase after a press release was issued and general practitioners were advised . The number of cases was too small to demonstrate the protective effect of early administration of benzylpenicillin . In five cases the consultant in communicable disease control was not informed for over 12 hours . Thirty-seven of the 48 index cases for whom information was available received rifampicin prophylaxis before discharge from hospital.

Ann N Y Acad Sci, 1994 Aug 15, 730, 209 - 16
Antiidiotype antibodies as surrogates for polysaccharide vaccines; Westerink MA et al.; In past studies we demonstrated that monoclonal antibody 6F9 is a surrogate image of the meningococcal C capsular polysaccharide . These studies indicated that immunization with this anti-id resulted in a T-dependent antibody response . In the studies reported in this paper, we show that the response which is elicited is protective . Using a model of meningococcal infection in BALB/c mice in which the animals are rendered susceptible with iron dextran, we studied the ability of this anti-id to protect adult mice against challenge . These studies encompassed the ability of 6F9 to prime neonatal mice and provide them with protection to later challenge . Adult BALB/c mice immunized with 6F9 had a 100% survival and a significantly reduced level of bacteremia at 24 hours . Neonatal mice primed within 24 hours of birth and immunized at 4 weeks of age with 6F9 had a 100% survival and cleared their bacteremia by 8 hours . Neonatal mice primed with 6F9 and challenged at 5 weeks had a 90% survival . These data indicate that anti-id 6F9 is a surrogate antigen for the meningococcal C polysaccharide and is capable of inducing protective immunity in immunologically mature as well as immature animals.

J Bacteriol, 1994 Aug, 176(15), 4583 - 9
Molecular cloning and analysis of genes for sialic acid synthesis in Neisseria meningitidis group B and purification of the meningococcal CMP-NeuNAc synthetase enzyme; Ganguli S et al.; The gene encoding for the CMP-NeuNAc synthetase enzyme of Neisseria meningitidis group B was cloned by complementation of a mutant of Escherichia coli defective for this enzyme . The gene (neuA) was isolated on a 4.1-kb fragment of meningococcal chromosomal DNA . Determination of the nucleotide sequence of this fragment revealed the presence of three genes, termed neuA, neuB, and neuC, organized in a single operon . The presence of a truncated ctrA gene at one end of the cloned DNA and a truncated gene encoding for the meningococcal sialyltransferase at the other confirmed that the cloned DNA corresponded to region A and part of region C of the meningococcal capsule gene cluster . The predicted amino acid sequence of the meningococcal NeuA protein was 57% homologous to that of NeuA, the CMP-NeuNAc synthetase encoded by E . coli K1 . The predicted molecular mass of meningococcal NeuA protein was 24.8 kDa, which was 6 kDa larger than that formerly predicted (U . Edwards and M . Frosch, FEMS Microbiol . Lett . 96:161-166, 1992) . Purification of the recombinant meningococcal NeuA protein together with determination of the N-terminal amino acid sequence confirmed that this 24.8-kDa protein was indeed the meningococcal CMP-NeuNAc synthetase . The predicted amino acid sequences of the two other encoded proteins were homologous to those of the NeuC and NeuB proteins of E . coli K1, two proteins involved in the synthesis of NeuNAc . These results indicate that common steps exist in the biosynthesis of NeuNAc in these two microorganisms.

Infect Immun, 1994 Aug, 62(8), 3391 - 5
Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults; Anderson EL et al.; A meningococcal vaccine containing group A and C polysaccharides conjugated to CRM197 was evaluated in 50 adults . Vaccinees were entered into one of five groups: 30 adults received a single dose of either 22, 11, or 5.5 micrograms of the conjugated A-C vaccine; 10 received an approved meningococcal vaccine; and 10 received saline injections . Local and systemic reactions to vaccines were recorded, and immune responses were determined . The experimental meningococcal vaccine was well tolerated, with the most frequent reaction being pain at the injection site . Both A and C polysaccharide components of the experimental vaccine were highly immunogenic, and total antibody concentrations 1 month postvaccination were not significantly different from the mean antibody concentrations among adults given the approved meningococcal vaccine . In addition, significant rises in immunoglobulin G, A, and M antibodies to both A and C polysaccharides occurred . Antibody concentrations measured at 6 and 12 months postvaccination had declined but remained significantly higher than prevaccination concentrations . Postvaccination meningococcal group C functional antibody activity increased more than 600-fold for both the polysaccharide and the conjugate vaccines . Further studies of this conjugated meningococcal vaccine are indicated for young children and infants.

J Infect Dis, 1994 Aug, 170(2), 453 - 6
Invasive disease caused by Neisseria meningitidis relatively resistant to penicillin in North Carolina; Woods CR et al.; A case of sepsis and meningitis caused by Neisseria meningitidis with relative resistance to penicillin occurred in North Carolina in August 1992 . This isolate was relatively resistant due to decreased affinity of its penicillin-binding protein 2 for penicillin . Such isolates have been reported in Spain, elsewhere in Europe, in South Africa, and in Canada, but invasive disease caused by meningococcal isolates relatively resistant to penicillin was not recognized in the United States before a preliminary report of this case in October 1992 . The Centers for Disease Control and Prevention recently retrospectively identified 3 additional cases from 1991 . A fifth case occurred in Kentucky in 1993 . Surveillance studies of penicillin susceptibility of N . meningitidis isolates suggest such meningococci have existed sporadically in the past . Increases in prevalence and magnitude of penicillin resistance among strains of N . meningitidis would require reconsideration of current clinical practice with regard to treatment of meningococcal disease.

J Infect Dis, 1994 Aug, 170(2), 449 - 53
Killing of meningococci by neutrophils: effect of vaccination on patients with complement deficiency; Schlesinger M et al.; To evaluate the in vitro effect of meningococcal vaccination, 3 C7-deficient (C7-D) siblings and 2 normal controls were studied before and 6 weeks after vaccination with treatment meningococcal vaccine (serogroups A, C, Y, and W) . Serobactericidal activity was not detected in the C7-D subjects and was low in the controls . Neither group was affected by vaccination . However, opsonized phagocytic killing increased significantly following vaccination in C7-D subjects and normal controls, despite only a modest increase in antimeningococcal titers . Heat inactivation of sera added to neutrophils resulted in low killing activity, which did not increase after vaccination . Thus, tetravalent meningococcal vaccine appears to enhance the phagocytic killing of meningococci in both normal and C7-deficient persons and should be given to all persons with C7 deficiencies.

Pediatr Infect Dis J, 1994 Aug, 13(8), 734 - 7
Surgical intervention for the complications of meningococcal-induced purpura fulminans; Herrera R et al.; Purpura fulminans is an infrequent but sometimes catastrophic illness that usually complicates a viral, rickettsial or bacterial infection . This communication presents a retrospective review of 152 patients with meningococcemia hospitalized at Children's Medical Center of Dallas from January, 1983, through December, 1993 . Eighteen (11.9%) of the 152 patients developed purpura fulminans . Thirteen (72%) of the 18 patients with purpura fulminans needed one or more surgeries including skin grafts, local debridement, microvascular flaps or amputations . Five patients (28%) died.

Zh Mikrobiol Epidemiol Immunobiol, 1994 Aug-Sep, Suppl 1, 44 - 8
{The Neisseria meningitidis serotypes and subtypes circulating among bacterial carriers in Moscow (1989-1991)}; Gorlina MKh et al.; N . meningitidis strains isolated from 218 healthy carriers in 1989-1991 in closed communities of adults, irrespective of cases of meningococcal infection registered in these communities, were characterized with a variety of different type and subtype antigens . Only in 139 strains (63.76%) their types and/or subtypes could be determined with the use of a set of 6 serotypes and 11 subtypes of monoclonal antibodies . 26 group B strains and 31 group C strains had multiple antigenic composition . 13 group A strains were found to be more homogeneous: 8 of them, isolated in one area, belonged, according to Dr . Achtman's data, to a definite clone VI-1, heretofore unknown . No prevailing serotype/subtype could be revealed, which reflected the wide heterogeneity of N . meningitidis at the period of the decrease of morbidity in meningococcal infection . The observed stability of serotype/subtype of strains, isolated from the same carriers and circulating in the same communities, suggests that the serotype/subtype of N . meningitidis is a valuable epidemiological marker.

FEMS Immunol Med Microbiol, 1994 Aug, 9(2), 135 - 42
Inhibitory effect of saliva from secretors and non-secretors on binding of meningococci to epithelial cells; Zorgani AA et al.; Carriage of Neisseria meningitidis B:4:P1.15 was higher among non-secretors during a school outbreak of meningitis; non-secretors had lower levels of anti-meningococcal salivary IgM . Flow cytometry was used to assess effects of secretor and non-secretor saliva on binding of B:4:P1.15 to buccal epithelial cells: (1) to assess inhibition by IgA and IgM; and (2) to assess contributions of salivary antibodies to inhibitory activities . Greater inhibition was obtained with secretor saliva: pooled (P = 0.049); fresh (P = 0.0001) . Purified IgA (P = 0.02) and IgM (P = 0.03) were equally inhibitory . After absorption of anti-meningococcal antibodies, there was still significant inhibitory activity in the pools: secretors (P = 0.018); non-secretors (P = 0.005) . These results indicate that both secretory immunoglobulins and other factors contribute to protection against colonisation by meningococci and might explain the increased carriage of B:4:1.15 in this population.

AACN Clin Issues Crit Care Nurs, 1994 Aug, 5(3), 278 - 88; quiz 411-3
Meningococcemia: recognizing and reducing complications in pediatric patients; Carno MA; Meningococcemia is a true infectious emergency that requires tremendous skill and collaboration among health-care professionals to reduce the high morbidity and mortality associated with this disease . Complications and sequelae may effect virtually every body system with meningococcal disease . The critical care nurse plays a crucial role in preventing and recognizing complications to reduce serious consequences, including respiratory distress syndrome, myocarditis, cardiovascular collapse, coagulopathies, major skin loss, and limb amputations.

Commun Dis Rep CDR Rev, 1994 Jul 22, 4(8), R85 - 90
The incidence of meningococcal illness in the East Anglian Regional Health Authority: 1990-1991; Laxton CE et al.; The rate at which notifications of meningococcal meningitis were reported by districts of the East Anglian Regional Health Authority to the Office of Population Censuses and Surveys (OPCS) varied between 6.8 and 28.0 cases per million resident population per year between 1987 and 1991 . A study was conducted to find out whether this variation represented differences in incidence, completeness of notification, or reporting practices . One hundred and one cases of meningococcal illness with onset between 1 January 1990 and 31 December 1991 were identified retrospectively in residents of the East Anglian region (population 2.06 million) . The ascertained incidence of meningococcal illness was 24.5 cases/million/year with a range between districts of 13.1 to 35.7 cases/million/year, similar to that expected from national data . Most of the variation in the rates of reporting to OPCS was explained by the practices of two consultants in communicable disease control (CCDCs), who reported all cases of which they were aware, irrespective of statutory notification . The study showed that communication to CCDCs was sometimes inadequate, and that control measures were not instituted in a small proportion of cases . The recommendations resulting from this study are, firstly, that OPCS should produce clear guidelines for notification and reporting . In the meantime proper officers should make their reporting practice explicit . Secondly, a sensitive case definition for meningococcal illness is needed for local monitoring of prophylactic coverage . Thirdly, CCDCs, microbiologists, clinicians, and environmental health officers should review arrangements for data exchange.

Infect Immun, 1994 Jul, 62(7), 2984 - 90
Immune responses in humans and animals to meningococcal transferrin-binding proteins: implications for vaccine design; Ala'Aldeen DA et al.; The results reported here show that the two meningococcal transferrin-binding proteins (TBP1 and TBP2) generate different immune responses in different host species and that there is variation in response dependent on the method of antigen preparation and possibly the route of administration . Mice immunized with either whole cells of Neisseria meningitidis SD (B:15:P1.16) or the isolated TBP1-TBP2 complex from the same strain produced antisera which, when tested against a representative panel of meningococcal isolates by Western blotting (immunoblotting), recognized some but not all heterologous TBP2 molecules . In contrast, rabbit antisera raised to the same preparations were cross-reactive with almost all the TBP2 molecules . The immune response to TBP1 was also host species dependent . Western blot analysis with denatured TBP1 failed to detect antibodies in antisera raised in mice to whole cells or in a rabbit to the TBP1-TBP2 complex but detected broadly cross-reactive antibodies in mouse anti-TBP1-TBP2 complex sera and strain-specific antibodies in rabbit anti-whole-cell serum . Human convalescent-phase sera obtained from five patients infected with meningococci of different serogroups and serotypes contained fully cross-reactive antibodies to TBP2 but no anti-TBP1 antibodies, when examined on Western blots . However, on dot immunoblots, the same patients' sera, as well as the mouse anti-whole cell and the rabbit anti-TBP1-TBP2 complex sera, reacted with purified biologically active TBP1 of strain SD . This indicates that native TBP1, a protein which loses its biological and some of its immunological activities when denatured, is immunogenic and that humans generate cross-reactive antibodies to native epitopes . These observations have important implications for assessing the vaccine potential of TBPs and other meningococcal antigens . Conclusions regarding the usefulness of TBPs as candidate components of meningococcal serogroup B vaccines based on results from certain animal species such as mice, or on methods such as Western blotting, may have little bearing on the situation in humans and may lead to some potentially useful antigens being disregarded.

Pathology, 1994 Jul, 26(3), 318 - 20
Serotype and serosubtype distribution of strains of Neisseria meningitidis isolated in South Australia and the Northern Territory of Australia: 1971-1989; Hansman D et al.; Strains of meningococci isolated from patients in South Australia (SA) and the Northern Territory (NT) with either bacteremia or meningitis (or both) were serotyped and serosubtyped using monoclonal antibodies in a whole cell ELISA technique . From SA, 144 isolates were examined for the period 1971 through 1989 and from the NT, 38 isolates from 1975 through 1977 and 1983 through 1989 were examined . During the periods of study the principal serogroups were group B in South Australia and group A in the Northern Territory . About 60% of the SA strains were typable and subtypable: the predominant types were 4, 2a, 15 and 14, in that order; the predominant subtypes were P1.2, P1.1 and P1.10, in that order . Of the strains from the NT about 80% were typable, the predominant type was type 4 and all 19 group A strains were identified as type 4, subtype P1.10.

Mol Microbiol, 1994 Jul, 13(2), 207 - 17
Variable expression of the Opc outer membrane protein in Neisseria meningitidis is caused by size variation of a promoter containing poly-cytidine; Sarkari J et al.; Opa proteins of Neisseria meningitidis exhibit translational phase variation via addition or deletion of repetitive coding repeat units within the DNA encoding the protein leader sequence . In contrast, Opc phase variation is the result of transcriptional regulation . Transcription starts 13 nucleotides after the -10 region of an unusual promoter sequence containing a variable number of contiguous cytidine residues and lacking a -35 region . Efficient expression of Opc occurred in strains with 12 to 13 cytidine residues, intermediate expression in strains with 11 or 14 residues and no expression with < or = 10 or > or = 15 residues . This unusual regulation may have evolved because the Opc protein enables meningococcal invasion and is immunogenic.

Ann Ital Med Int, 1994 Jul-Sep, 9(3), 173 - 7
The role of complement in anti-bacterial defence; D'Amelio R et al.; The complement system consists of several proteins present in human serum interacting among themselves and with the other compounds of the immune system in the host defence process . In particular, late complement component (C5, C6, C7, and C8) deficiencies (LCCD) are closely associated with Neisseria, mainly meningitidis, infections . The aim of our study was to verify this association in an Italian population by analyzing the complement profile in survivors of meningococcal meningitis . Ten out of the 59 (17%) subjects studied had homozygous LCCD (6 C8, 3 C7 and 1 C6) . The meningococcal C strain was the most widely diffused (68%) and had infected all homozygous LCCD subjects . In addition meningococcal serogroup C seemed to be the least immunogenic when compared to serogroups A and B . These data confirm the close association between homozygous LCCD and meningococcal infections from common serogroups (A, B and C) in the Italian population . Anti-meningococcal vaccination is usually recommended for LCCD subjects because it increases, both quantitatively and qualitatively, the antibody component of anti-meningococcal immune defence . We therefore analyzed the levels of anti-polysaccharide (PS) A and PSC antibodies in the members of 4 families including normal subjects and subjects with homozygous and heterozygous C7, C8 or factor H defects, before and after vaccination with only PSA+C . Surprisingly, we found the highest levels of antibodies before vaccination in homozygous subjects, followed by heterozygous and normal controls, whereas, after vaccination, homozygous subjects showed the lowest increase of specific antibodies, indicating their relative incapacity to respond to meningococcal PS alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Rev Med Brux, 1994 Jul-Aug, 15(4), 166 - 71
{Vaccinations and useful advice for travelers}; Van Laethem Y; International travels are increasingly frequent . Beside malaria prophylaxis, the general practitioner will review several vaccinations.e Tetanus and poliomyelitis vaccines should be administered once every ten years . It will often be useful to give a protection against hepatitis A, and less often, against typhoid fever . The yellow fever vaccine, which may be required or recommended to visit several African and South American countries, is injected only by officially recognised centres . For some travels, vaccination against hepatitis B, meningococcal meningitis or, rarely, against rabies may be considered . The vaccine against cholera will never be administered, due to its lack of efficacy and high frequency of side effects . Travellers diarrhoea will be discussed, and a "pocket" treatment prescribed . Finally, general information will be provided, including those on STD.

J Clin Microbiol, 1994 Jul, 32(7), 1783 - 7
Characterization of epidemic Neisseria meningitidis serogroup C strains in several Brazilian states; Sacchi CT et al.; Epidemic strains of the Neisseria meningitidis C:2b:P1.3 electrophoretic type 11 complex were responsible for an outbreak in Curitiba, Parana State, Brazil, from 1990 to 1991 . Strains of this complex were also isolated in other Brazilian states and were responsible for a meningococcal disease epidemic in Sao Paulo State in 1990 . Serotyping both with monoclonal antibodies and by multilocus enzyme electrophoresis was useful for typing these epidemic strains related to the increased incidence of meningococcal disease . The genetic similarity of members of the electrophoretic type 11 complex was confirmed by the ribotyping method by using EcoRI or ClaI endonuclease restriction enzymes.

Rev Inst Med Trop Sao Paulo, 1994 Jul-Aug, 36(4), 301 - 10
Induction of iron regulated proteins during normal growth of Neisseria meningitidis in a chemically defined medium; Brandileone MC et al.; The expression of iron regulated proteins (IRPs) in vitro has been obtained in the past by adding iron chelators to the culture after bacterial growth, in the presence of an organic iron source . We have investigated aspects concerning full expression of the meningococcal IRPs during normal growth, in defined conditions using Catlin medium, Mueller Hinton and Tryptic Soy Broth (TSB) . The expression of IRPs varied between different strains with respect to Ethylenediamine Di-ortho-Hidroxy-phenyl-acetic acid (EDDA) concentrations, and according to culture medium, and also between different lots of TSB . For each strain, a specific set of IRPs were expressed and higher EDDA concentrations, or addition of glucose, or use of different culture media did not resulted in a differential expression of IRPs . We were not able to grow N . meningitidis under normal growth conditions using Desferal . We looked for a good yield of outer membrane vesicles (OMVs) expressing IRPs in iron-deficient Catlin medium containing EDDA and Hemin . Culture for 32 h at 30 degrees C after growing for 16 h at 37 degrees C supported good bacterial growth . Bacterial lysis was noted after additional 24 h at 30 degrees C . Approximately 4 times more OMVs was recoverable from a culture supernatant after 24 h at 30 degrees C than from the cells after 16 h at 37 degrees C . The IRP were as well expressed in OMVs from culture supernatant obtained after 24 h at 30 degrees C as from the cells after 16 h at 37 degrees C.

Infect Immun, 1994 Jul, 62(7), 2947 - 52
Tn916-generated, lipooligosaccharide mutants of Neisseria meningitidis and Neisseria gonorrhoeae; Stephens DS et al.; A library of Tn916-generated, tetracycline-resistant (Tc) mutants of the group B Neisseri meningitidis strain NMB was screened by using monoclonal antibodies (MAbs) that recognize structural differences in neisserial lipooligosaccharide (LOS) . The LOS of parental strain NMB had a relative molecular mass of 4.5 kDa, reacted with MAbs 3F11 and 6B4 but not with MAb 4C4 or 6E4, and contained a lacto-N-neotetrose unit . Two phenotypically stable mutants, SS3 and R6, altered in LOS, were identified by colony immunoblots, electrophoresis, and Western immunoblots . The LOS of mutant SS3 was 3.4 kDa and reacted with MAbs 4C4 and 6E4 but not MAb 3E11 or 6B4 . The LOS of mutant R6 was 3.1 to 3.2 kDa and reacted with MAb 6E4 but not MAb 3F11, 6B4, or 4C4 . Thus, the LOSs of the R6 and SS3 mutants were predicted to contain different truncations of the core oligosaccharide . The LOS phenotype of each mutant was linked to Tc(r), as determined by transformation of the parent strain with DNA from the mutant . Southern hybridizations and single-specific-primer PCR revealed in each mutant a single truncated tn916 insertion which had lost genes required for mobilization . Tn916 mutagenesis was used to identify two distinct genetic sites in the meningococcal chromosome involved in biosynthesis of the oligosaccharide chain of LOS and to create genetically defined LOS mutants of N . meningitidis and Neisseria gonorrhoeae.

J Infect Dis, 1994 Jun, 169(6), 1384 - 9
Use of arbitrarily primed polymerase chain reaction analysis to type disease and carrier strains of Neisseria meningitidis isolated during a university outbreak; Woods JP et al.; Disease and carrier isolates of Neisseria meningitidis from two regions of the United States were typed by the arbitrarily primed polymerase chain reaction (PCR), or random amplified polymorphic DNA (RAPD), method . This technique generates strain-specific arrays of amplified DNA fragments using low-stringency PCR with single, arbitrarily chosen primers . Each of 3 disease isolates and 7 of 11 carrier isolates from an outbreak at the University of Connecticut were indistinguishable using each of 4 primers . In contrast, 22 other isolates (the remaining 4 carrier isolates plus 18 disease and carrier isolates from Connecticut, Illinois, and Missouri) were divided into 18 sets using the same 4 primers . This outcome supports the view that disease isolates from an outbreak may reflect sporadic invasive progression by a strain that also frequently causes asymptomatic colonization . Our results show that RAPD tests provide a sensitive and efficient means of distinguishing genetically different meningococcal strains and that they should facilitate clinical, epidemiologic, and population genetic studies of this important pathogen.

Microbiology, 1994 Jun, 140 ( Pt 6), 1473 - 80
Isolation and characterization of the haemin-binding proteins from Neisseria meningitidis; Lee BC; The mechanism of haem-iron acquisition in Neisseria meningitidis is poorly understood . Using haemin-agarose in a batch affinity chromatography method, two haemin-binding proteins of 97 and 50 kDa were isolated from total membranes derived from Neisseria meningitidis B16B6 grown under iron-deficient but not under iron-replete conditions . No binding proteins were affinity-purified when total membranes underwent limited proteolysis with trypsin, suggesting a haem-protein interaction . When biotinylated human haemoglobin was used as the affinity ligand, proteins of identical molecular mass were isolated . Detection of haemin-binding proteins in a whole cell binding assay demonstrated a surface-exposed location . Competitive binding studies indicated that this haem-protein interaction was specific, because only haemin or human haemoglobin, but not cytochrome c111, protoporphyrin IX, iron-loaded human lactoferrin, iron-loaded human transferrin or Fe(NO3)3, could abrogate binding . The presence of similar haemin-binding proteins in a limited survey of clinical meningococcal strains indicated that the expression of the haemin-binding proteins is not serogroup-specific.

J Clin Microbiol, 1994 Jun, 32(6), 1475 - 82
Multicenter comparison of Neisseria meningitidis serogroup C anti-capsular polysaccharide antibody levels measured by a standardized enzyme-linked immunosorbent assay; Gheesling LL et al.; A standardized enzyme-linked immunosorbent assay (ELISA) was used by 11 laboratories to measure levels of total serum antibody to Neisseria meningitidis serogroup C capsular polysaccharide in 16 unpaired pre- and postvaccination serum samples . Twelve serum samples were from adults, and four were from children aged 2, 3, 5, and 9 . The between-laboratory coefficient of variation for pre- and postvaccination sera ranged from 16 to 59% and 11 to 21%, respectively . The average percent difference (absolute value) from the between-laboratory means for all prevaccination sera measured by each laboratory was 24%, whereas the average percent difference was 13% for all postvaccination sera . A postvaccination quality control serum was diluted three times to give optical densities on the high, middle, and low portions of the standard reference curve . The three dilutions were assayed by the 11 laboratories a total of 241 times and yielded an overall coefficient of variation of 20% . Antibody-binding inhibition curves showed that the standardized ELISA was specific for N . meningitidis serogroup C capsular polysaccharide antibody . Fifty percent inhibition of seven serum samples was obtained after reaction with an average concentration of 0.9 micrograms of meningococcal serogroup C polysaccharide per ml; an average of 93% inhibition was obtained with 50 micrograms of polysaccharide per ml . The acceptance and use of this standardized ELISA will reduce between-laboratory assay variability and ensure a more accurate and reproducible assessment of immunogenicity for vaccines under development.

An Med Interna, 1994 Jun, 11(6), 291 - 3
{Apropos a case of primary meningococcal arthritis in an adult}; Omar M et al.; We present the case of a 52-years-old patient which was diagnosed of septic primary meningococcal arthritis, being acute arthritis the only form of presentation without any other manifestations of the meningococcal disease . We want to stress that despite the low frequency of this disease, especially in the adult, it must be taken into account for the assessment of acute mono-oligoarthritis.

Infect Immun, 1994 May, 62(5), 1755 - 60
Analysis of C3 deposition and degradation on Neisseria meningitidis and Neisseria gonorrhoeae; Jarvis GA; The deposition and degradation of human complement component C3 on the cell surfaces of Neisseria meningitidis and Neisseria gonorrhoeae were studied . Bacteria were incubated in human serum, and ester-linked C3 fragments were analyzed by hydroxylamine release and immunoblot detection . Similar patterns of C3 degradation were found for both serum-resistant and serum-sensitive meningococcal strains of serogroups A, B, C, Y, and W135, as well as for serum-sensitive gonococcal strains and their sialylated serum-resistant variants . The predominant fragments in all cases were the 40-kDa alpha' 2 chain of iC3b and the 75-kDa beta chain common to both C3b and iC3b . The 67-kDa alpha' 1 chain of iC3b was also detected . The 105-kDa alpha' chain of intact C3b represented a minor proportion of deposited C3 . Capsule-specific immunoglobulin G or immunoglobulin A1 did not alter the observed degradation patterns, nor did incubation of meningococci in properdin-deficient serum . The degradation of C3 in C5-, C6-, or C8-deficient serum was the same as that in normal serum, although the deposition of C3 was severely limited, based as indicated by the intensity of the fragments . With the use of an enzyme-linked immunosorbent assay that measured total iC3b and C3, I found that both iC3b deposition and C3 deposition varied among meningococcal and gonococcal strains and that the amounts of iC3b and C3 were independent of the relative quantities of cell surface sialic acid and of serum sensitivity for meningococci but not for gonococci . I conclude that complement activation on neisserial cell surface results in the formation of an identical repertoire of predominantly iC3b fragments of ester-linked C3b molecules regardless of the presence of sialic acid in either the capsule or the lipooligosaccharide or of the sensitivity of the organism to complement-mediated lysis but that the quantities of both ester- and amide-linked iC3b molecules deposited exhibit strain variability.

Eur J Clin Microbiol Infect Dis, 1994 May, 13(5), 388 - 93
Characterization of Neisseria meningitidis isolates and clinical features of meningococcal conjunctivitis in ten patients; Anderson J et al.; Cases of meningococcal conjunctivitis occurring in Denmark in the period 1982-1991 were reviewed . In a survey of laboratory reports, ten cases were identified . The meningococcal strains were characterized by serological grouping, typing and subtyping, and by antimicrobial susceptibility testing . Five cases were caused by serogroup B meningococci (B:15:P1.16, B:15:P1.6, B:4:P1.15) and five cases by serogroup C meningococci (C:2a:P1.2 (4 strains), C:14:NST) . The median age of the patients was 12.5 months (range 7 days to 9 years) . Signs of conjunctivitis were predominant; in addition, five of the patients had fever and general malaise . In one patient the same strain was recovered from blood and eye secretions . None of the patients had signs of meningitis . All meningococcal strains isolated from patients with meningococcal conjunctivitis were assumed to be virulent and had the same characteristics as strains causing meningococcal disease in Denmark within the same period.

Eur J Pediatr, 1994 May, 153(5), 367 - 8
Spinal cord dysfunction in neonatal meningococcal meningitis; Kirkpatrick M et al.; A 3-week-old infant with meningococcal meningitis is described whose clinical course was complicated by paraparesis and urinary retention . This rare complication of meningococcal meningitis has not previously been reported in the neonatal age group.

J Clin Pathol, 1994 May, 47(5), 405 - 10
Two enzyme linked immunosorbent assays for detecting antibodies against meningococcal capsular polysaccharides A and C; Akinwolere OA et al.; AIMS--To evaluate two of the recent methods of coating microtitre plates in the enzyme linked immunosorbent assay (ELISA) for detecting human antibodies against meningococcal capsular polysaccharides A and C with a view to validating a specific meningococcal antibody assay for routine clinical use . METHODS--Two four-layer ELISA protocols were standardised: one method utilised meningococcal polysaccharides conjugated to poly-L-lysine polypeptide for coating the microtitre plates; another used polysaccharides mixed with methylated human serum albumin (mHSA) . Titration curves were plotted for the ELISAs and the squared Pearson correlation coefficient (R2) was used to determine the degree of accuracy of fit of the curves . Specificity tests were performed by inhibition and adsorption studies . RESULTS--Both methods gave good titration curves with a high R2 of > 0.98, indicating a high degree of accuracy in forming the curves . The titration end point after vaccination, obtained by the mHSA method, was 20 times higher, however, than that obtained by the poly-L-lysine method . Specificity tests showed that in the ELISA using polysaccharide/poly-L-lysine, antibody activity of a pre-vaccination serum sample was inhibited by 37%, and of post-vaccination serum by 50% with 1000-fold excess antigen . Antibody activity (post-vaccination) was reduced by 51% and 59%, respectively, by adsorption with antigen-coated Sepharose beads or adsorption with suspensions of killed meningococci . In contrast, antibody activity of a pre-vaccination serum was inhibited by 60% and a post-vaccination serum by 90% in ELISA employing polysaccharides mixed with mHSA . Reproducibility was better with the use of methylated human serum albumin than with poly-L-lysine; the former showed intrabatch and interbatch coefficients of variation of 4% and 2%, respectively, compared with 43% (intrabatch) and 16% (interbatch) obtained with the poly-L-lysine . CONCLUSION--It is concluded that the antibody assay using meningococcal polysaccharides groups A and C mixed with mHSA is much better than that using polysaccharides coupled with poly-L-lysine.

Sante, 1994 May-Jun, 4(3), 237 - 41
{Vaccination perspectives}; Saliou P et al.; The aim of vaccinology is to improve the available vaccines and to develop new ones in the light of progress in immunology, molecular biology and biotechnologies . But it must go beyond this, and aim to protect all populations and control diseases, even eradicate them where possible . New vaccine strategies must be developed taking into account the epidemiology of diseases and the inherent logistic problems of implementing these strategies under local conditions . There are three major thrusts to the progress of the discipline . The improvement of the vaccines available . One of the drives of vaccinology is not only to deliver vaccines of increasing safety (replacement of the current vaccine for whooping cough with an acellular vaccine for example), but also to improve vaccine efficacy and immunogenicity (in particular for flu, tuberculosis, cholera and rabies vaccines) . The optimisation of vaccination programmes and strategies for vaccinations . The ideal is to protect against the greatest possible number of diseases with the smallest number of vaccinations . The development of combinations of vaccines is central to this goal . The objective for the year 2000 is a hexavalent vaccine DTPP Hib HB . The development of new vaccines . Classic techniques continue to be successfully used (inactivated hepatitis A vaccine; attenuated live vaccines for chicken pox and dengue fever; conjugated polyosidic bacterial vaccines for meningococci and Streptococcus pneumoniae) . However, it will become possible to prepare vaccines against most transmissible diseases using genetic engineering techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Sante, 1994 May-Jun, 4(3), 231 - 6
{Epidemiological and control aspects of meningococcal meningitis epidemics in Africa}; Spiegel A et al.; Meningococcal meningitis epidemics are a major health problem in sub-saharan Africa where they account for thousands of deaths and cause morbidity in hundreds of thousands of people . Meningitis is caused by Neisseria meningitidis . In Africa, epidemic meningitis is primarily due to strains of serogroup A which are responsible for the largest and most recent epidemics . N . meningitidis serotype 4, serosubtype P1.9, clonal complex III-1 was introduced into Africa in 1987 . Since then, epidemics spread through the Lapeyssonnie's meningitis belt to the south . Classically, the 6 months-30 years old age group is the group at highest risk of disease . Nevertheless, in recent epidemics caused by clonal complex III-1, high age-specific attack rate occurred in those aged 30 years and over . The objectives of epidemic control are the reduction of mortality and morbidity . Early detection of an emerging epidemic is based on the observation of an incidence rate above a cutoff value . Recently, the WHO has proposed a cutoff of 15 cases/100,000/week averaged over two weeks . Epidemic investigation must be as rapid as possible after detection . The different steps are: confirmation of the epidemic and the meningococcal aetiology, standard case definition and determination of the high risk population . During epidemics, in developing countries, simplified treatment protocols are justified and a single dose of long-acting chloramphenicol is a useful first-line treatment . The strategy most frequently used for the control of epidemics is mass vaccination after the start of the epidemic . This must be done as quickly as possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Shock, 1994 May, 1(5), 317 - 24
Continued tumor necrosis factor receptor expression by trauma patients' monocytes (Mphi) despite TNF alpha secretion; Miller-Graziano CL et al.; In investigating various mechanisms for continued elevated tumor necrosis factor alpha (TNF alpha) production in trauma patients' monocytes (Mphi), we examined TNF receptor (TNFR) levels on the patients' Mphi as a possible altered pathway leading to continued autocrine TNF alpha stimulation . Mphi TNFR synthesis and shedding are both increased as TNF alpha protein production increases . In fatal meningococcal infections, TNFR shedding fails to pace TNF alpha production . Here, isolated normal and trauma patients' Mphi (injury severity score greater than 30), were examined by flow cytometry using phycoerythrin-labeled TNF alpha to detect increased or decreased TNFR expression concomitant to Mphi production of secreted TNF alpha (as measured in the LM bioassay) . Immunoaberrant patients (mitogen proliferation depressed) had reduction in detectable TNF alpha binding by their TNFR, while Mphi from immunocompetent (normal mitogen response) trauma patients' Mphi had a TNFR expression intensity comparable to normals' Mphi . Upon in vitro stimulation of TNF alpha (IFN gamma + muramyl dipeptide) normals' and immunocompetent patients' MO TNFR expression is decreased for the entire 18 h period during which secreted TNF alpha is produced, but immunoaberrant trauma patients' Mphi increased their TNFR expression, while concomitantly producing both secreted and cell-associated TNF alpha protein . Patients' Mphi with highly elevated TNF alpha levels are still expressing high levels of TNFR and capable of auto-stimulating TNF alpha production . This elevated TNFR expression could be due to reduced shedding, overproduction of TNFR, or both.

Vaccine, 1994 May, 12(6), 535 - 41
Vaccine potential of meningococcal FrpB: studies on surface exposure and functional attributes of common epitopes; Ala'Aldeen DA et al.; Neisseria meningitidis expresses several novel outer membrane proteins (OMPs) in vivo and when grown under iron limitation in vitro . One of the most prominent is a 70 kDa iron-regulated protein (FrpB) . FrpB was purified by elution from SDS-polyacrylamide gels and rabbit polyclonal antiserum (R-70) was raised against it . R-70 was bactericidal against homologous, but not heterologous, strains in the presence of human complement . The bactericidal activity was retained when R-70 was adsorbed with formaldehyde-fixed iron-replete cells (i.e . not expressing FrpB), but lost when absorbed with fixed iron-restricted cells (which express FrpB) . A murine monoclonal anti-FrpB antibody (mAb M70) was raised against a common epitope which showed complete cross-reaction on Western blots of OMPs from other serogroups and serotypes of N . meningitidis and some commensal Neisseriae species . However, it failed to kill the organism . Immunogold electron microscopy on ultrathin sections, using the R-70 antiserum adsorbed with fixed iron-replete cells, showed labelling on 40% of the cells, whereas the R-70 adsorbed with fixed iron-restricted cells and mAb M70 failed to label . However, none of these sera labelled whole cells, suggesting lack of surface accessibility . It appears that the highly conserved cross-reactive epitopes of FrpB only become exposed in the process of generating the antigen, whereas the surface-exposed epitopes recognized in killing assays are immunologically variable among different strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Infect Immun, 1994 May, 62(5), 1566 - 75
Meningococcal group A lipooligosaccharides (LOS): preliminary structural studies and characterization of serotype-associated and conserved LOS epitopes; Kim JJ et al.; Structural studies indicate that the neisserial lipooligosaccharides (LOS) are composed of an oligosaccharide (OS) portion with a phosphorylated diheptose (Hep) core attached to the toxic lipid A moiety . A conserved meningococcal LOS epitope, defined by monoclonal antibody (MAb) D6A, is expressed on group A and many group B and C meningococci of different LOS serotypes (J . J . Kim, R . E . Mandrell, H . Zhen, M . A . Apicella, J . T . Poolman, and J . M . Griffiss, Infect . Immun . 56:2631-2638, 1988) . This MAb-defined D6A epitope is immunogenic in humans (M . M . Estabrook, R . E . Mandrell, M . A . Apicella, and J . M . Griffiss, Infect . Immun . 58:2204-2213, 1990; M . M . Estabrook, C . J . Baker, and J . M . Griffiss, J . Infect . Dis . 197:966-970, 1993) . In this study, we characterize this important MAb-defined LOS epitope . Serotype L10 and L11 group A meningococal LOS were chemically modified and used to investigate what portion of the LOS molecule is important for expression of the conserved (D6A) epitope and serotype-associated LOS epitopes by use of immunoblotting techniques and selected MAbs as probes . Preliminary structural characterization of the LOS was also accomplished by electrospray ionization-mass spectrometry . Our results indicate the following . (i) Antibodies that recognize the serotype-associated or conserved LOS epitopes recognize the OS portion of the LOS . (ii) The phosphorylated diheptose core region of the OS is essential for expression of the conserved D6A epitope . (iii) The lipid portion of the molecule is important for optimum expression of the LOS epitopes . (iv) The proposed compositions of the O-deacylated LOS are consistent with the presence of a phosphorylated diheptose core and are as follows: for O-deacylated L10 LOS, 3Hex (hexose), 1HexNAc (N-acetylhexosamine), 2KDO (2-keto-3-deoxy-D-manno-octulosonic acid), 2Hep (heptose), 1PEA or 2PEA (phosphoethanolamine), and O-deacylated lipid A; and for O-deacylated L11 LOS, 2Hex, 1HexNAc, 2KDO, 2Hep, 2PEA, and O-deacylated lipid A . Because the phosphorylated diheptose core region of the LOS is essential for the formation of a conserved LOS epitope (D6A) that is immunogenic in humans, care should be taken to maintain stereochemical requirements for the expression of this conserved epitope in the design of effective, nontoxic LOS vaccines.

Epidemiol Infect, 1994 Apr, 112(2), 315 - 28
Smoking, the environment and meningococcal disease: a case control study; Stanwell-Smith RE et al.; This case control study investigated environmental factors in 74 confirmed cases of meningococcal disease (MD) . In children aged under 5, passive smoking in the home (30 or more cigarettes daily) was associated with an odds ratio (OR) of 7.5 (95% confidence interval (CI) 1.46-38.66) . ORs increased both with the numbers of cigarettes smoked and with the number of smokers in the household, suggesting a dose-response relationship . MD in this age group was also significantly associated with household overcrowding (more than 1.5 persons per room) (OR 6.0, 95% CI 1.10-32.8), with kisses on the mouth with 4 or more contacts in the previous 2 weeks (OR 2.46, 95% CI 1.09-5.56), with exposure to dust from plaster, brick or stone in the previous 2 weeks (OR 2.24, 95% CI 1.07-4.65); and with changes in residence (OR 3.0, 95% CI 1.0-8.99), marital arguments (OR 3.0, 95% CI 1.26-7.17) and legal disputes in the previous 6 months (OR 3.10, 95% CI 1.24-7.78) . These associations were independent of social class . Public health measures to lower the prevalence of cigarette smoking by parents of young children may reduce the incidence of MD . The influence of building dust and stressful life events merits further investigation.

J Infect Dis, 1994 Apr, 169(4), 847 - 52
Duration of antibody response after meningococcal polysaccharide vaccination in US Air Force personnel; Zangwill KM et al.; The long-term kinetics of the immunologic response after vaccination of adults with Neisseria meningitidis polysaccharide vaccine is unknown . Total meningococcal anti-capsular antibody response (measured by ELISA) and serum bactericidal activity after routine vaccination with quadrivalent meningococcal vaccine were evaluated in US Air Force personnel . In a retrospective cross-sectional study, blood samples were obtained from approximately 40 personnel before vaccination, at 1 and 4-6 months, and at 2, 3, 4, 6, 8, and 10 years after vaccination . Total anti-group A and -group C capsular antibody levels and bactericidal activity peaked 1 month after vaccination and declined substantially by 2 years . At each interval, significantly higher levels of total antibody and bactericidal activity were detected than before vaccination . Anti-capsular antibodies and bactericidal activity persisted for up to 10 years after immunization . These and further studies on the serologic measure of protection against meningococcal disease are important for evaluation of candidate vaccines and development of recommendations for immunization.

Infect Immun, 1994 Apr, 62(4), 1437 - 43
Humoral immune response to class 1 outer membrane protein during the course of meningococcal disease; Guttormsen HK et al.; We have determined the amounts of specific anti-class 1 outer membrane protein antibodies in sera from 25 patients during the course of systemic meningococcal disease, using purified class 1 protein as the sensitizing antigen in an enzyme-linked immunosorbent assay . The class 1 protein was obtained from a variant of strain 44/76 (B:15:P1.7,16) lacking class 3 and class 4 outer membrane proteins . Specific anti-class 1 (serosubtype P1.7,16) outer membrane protein immunoglobulin G (IgG) antibody levels increased significantly in 12 patients (12 of 25; 48%), regardless of the serotype of the infecting strain, indicating that the antibodies reacted in part with epitopes not determined by the monoclonal antibodies used for serotyping . Most patients had low levels of anti-class 1 IgG antibodies during the acute illness . The antibody levels peaked during the second week of disease and returned to near baseline levels in sera collected 6 weeks to 12 months after the onset of the disease . The majority of the specific anti-class 1 IgG antibodies bound to surface-exposed epitopes on whole bacteria and belonged to the IgG1 and IgG3 subclasses . Anti-class 1 IgA and IgM antibodies were not detected in any of the patient sera . Prior to disease, seven patients had been immunized with a meningococcal outer membrane vesicle vaccine developed from strain 44/76 (P1.7,16) . None of these patients was infected with meningococcal strains containing class 1 protein homologous or partly homologous to that of the vaccine strain, indicating serosubtype-specific protection . The highest anti-class 1 IgG antibody peak levels were seen in immunized patients infected with strains of heterologous serotype, suggesting an anamnestic response . However, these patients were not protected from meningococcal disease after immunization.

Mol Microbiol, 1994 Apr, 12(2), 253 - 65
The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation; Suker J et al.; Molecular analyses were applied to the genes encoding variants of the serosubtyping antigen, the class 1 outer membrane protein (PorA), from 55 serogroup A Neisseria meningitidis strains . These genes were evolutionarily stable and exhibited a limited range of genetic variation, primarily generated by recombination . Translation of the gene sequences revealed a total of 19 distinct amino acid sequences in the variable regions of the protein, 6 of which were not recognized by currently available serosubtyping monoclonal antibodies . Knowledge of these amino acid sequences permitted a rational re-assignment of serosubtype names . Comparison of the complete genes with porA gene sequences from serogroup B and C meningococci showed that serogroup A possessed a limited number of the possible porA genes from a globally distributed gene pool . Each serogroup A subgroup was characterized by one of four porA gene types, probably acquired upon subgroup divergence, which was stable over periods of decades and during epidemiological spread . Comparison with other variable genes (pil and iga) indicated that the three alleles were independently assorted within the subgroup, suggesting that their gene types were older than the subgroups in which they occurred.

Mol Microbiol, 1994 Apr, 12(2), 171 - 80
Microevolution within a clonal population of pathogenic bacteria: recombination, gene duplication and horizontal genetic exchange in the opa gene family of Neisseria meningitidis; Hobbs MM et al.; Opacity (Opa) proteins are a family of antigenically variable outer-membrane proteins of Neisseria meningitidis . Even among clonally related epidemic meningococcal isolates, there is greater variation of Opa protein expression than can be accounted for by the opa gene repertoire of any individual strain . We characterized the opa genes of eight closely related isolates of serogroup A N . meningitidis (subgroup IV-1) from a recent meningitis epidemic in West Africa . DNA sequence analysis and Southern blot experiments indicated that changes occurred in the opa genes of these bacteria as they spread through the human population, over a relatively short period of time . Such changes in one or a few loci within a clonal population are referred to as microevolution . The distribution of sequences present in hypervariable (HV) regions of the opa genes suggests that duplication of all or part of opa genes into other opa loci changed the repertoire of Opa proteins that could be expressed . Additional variability in this gene family appears to have been introduced by horizontal exchange of opa sequences from other meningococcal strains and from Neisseria gonorrhoeae . These results indicate that processes of recombination and genetic exchange contributed to variability in major surface antigens of this clonal population of pathogenic bacteria.

Vopr Med Khim, 1994 Mar-Apr, 40(2), 33 - 4
{Antioxidant activity of blood serum and blood enzymes in meningococcal infections in children and adults}; Roslyi IM; Aspartate transaminase activity (AST) was measured in the serum of children and adults suffering from generalized meningococcal infection . Activation of AST is only rarely detected in children, which is associated with higher protection from lipid peroxidation . The ratio between antioxidants and prooxidants was higher in children than in adults.

J Infect Dis, 1994 Mar, 169(3), 673 - 6
Phenotypic and genotypic changes in a new clone complex of Neisseria meningitidis causing disease in The Netherlands, 1958-1990; Scholten RJ et al.; To characterize the phenotypic and genotypic changes that occurred in a new clone lineage of Neisseria meningitidis (lineage III) in the Netherlands, the electrophoretic type (ET) was determined for 79 serogroup B isolates of serotype 4 or subtype P1.4 (or both) obtained between 1958 and 1990 from patients with systemic meningococcal disease . Thirty-five previously described isolates were also included . After its appearance in 1980, lineage III started homogeneously with regard to both genotype (ET-24) and phenotype (B:4:P1.4) . After 1984, other clones appeared in the lineage, and the various clones acquired other serotypes (serotypes 14 and 15) and subtypes (P1.2, P1.7, and P1.12), indicating frequent exchange of genetic material between clones . These results indicate that basing a serogroup B vaccine on outer membrane components from a single strain is not a valid strategy for the prevention of meningococcal disease.

J Nucl Med, 1994 Mar, 35(3), 469 - 70
Pericardial and myocardial localization of antimyosin in a case of acute myocarditis; Castell J et al.; A 60-yr-old immunodepressed woman presented with acute perimyocarditis and cardiac tamponade complicating meningococcic infection . We had the opportunity to study her cardiac condition by injecting antimyosin during the acute phase . Images at 48 hr showed unexpected findings, with obvious localization of the tracer in the pericardial fluid, as well as myocardial uptake . Possible mechanisms for pericardial activity are discussed.

J Bacteriol, 1994 Mar, 176(5), 1530 - 4
Identification of a genetic locus involved in the biosynthesis of N-acetyl-D-mannosamine, a precursor of the (alpha 2-->8)-linked polysialic acid capsule of serogroup B Neisseria meningitidis; Swartley JS et al.; We characterized the genetic defect of a capsule-deficient serogroup B meningococcal strain created by Tn916 mutagenesis . The transposon insertion interrupts a capsule biosynthesis gene, synX, which is involved in the production of N-acetyl-D-mannosamine, a precursor of the (alpha 2-->8)-linked polysialic acid capsule of serogroup B meningococci.

Infection, 1994 Mar-Apr, 22(2), 69 - 71
First recorded outbreaks of meningococcal disease in the Israel Defence Force: three clusters due to serogroup C and the emergence of resistance to rifampicin; Almog R et al.; Outbreaks of meningococcal disease were observed for the first time in the Israel Defence Force (I.D.F.) in 1992 and 1993, while in previous years, cases appeared in sporadic fashion . Two episodes in the winter of 1992 involving three and two individuals, respectively, were caused by Neisseria meningitidis group C, which was nontypable and nonsubtypable (C:NT:-) . Three cases in one event in early 1993 were due to group C:NT:P1.2, the two secondary cases being caused by strains completely resistant to rifampicin . While these outbreaks were small, they should be seen against a background of the emergence of relatively virulent clones of serogroup C which have caused significant outbreaks in several countries . This and the drug resistance problem will require medical decision-makers to review strategies for the prevention of meningococcal disease, taking into account alternative agents for chemoprophylaxis as well as a possible role for vaccination.

J Infect, 1994 Mar, 28(2), 199 - 207
Meningococcal disease in childhood--a regional study in Ireland; Fogarty J et al.; A retrospective study of microbiology laboratory records of culture-confirmed cases of meningococcal disease in children under 14 years of age, admitted to four Dublin hospitals, was conducted for the period 1981-1991 inclusive . The study aimed to describe the epidemiology of meningococcal disease in childhood and to assess the potential of meningococcal group A and C vaccine in preventing disease . There were 406 cases of meningococcal disease of which 319 (78.6%) were in children under 5 years of age . The meningitis to septicaemia ratio was almost 4:1 (320 vs . 86 cases) . Of the 406 cases, 216 (53.2%) cases occurred during the period November to March . The age-specific annual incidence rates for the Eastern Health Board region served was 64.2 per 100,000 under 1 year of age and 24.6 per 100,000 under 5 years of age . A relative increase in disease caused by meningococcal serogroup C was observed during the period of the study . Only 15% all cases could have been prevented by a policy of universal meningococcal group A and C immunisation at 2 years of age . Such a policy, therefore, is not recommended . A vaccine for preventing disease caused by meningococcal group B is urgently required.

Mol Microbiol, 1994 Mar, 11(5), 885 - 96
Contribution of genes from the capsule gene complex (cps) to lipooligosaccharide biosynthesis and serum resistance in Neisseria meningitidis; Hammerschmidt S et al.; Within the capsule gene complex (cps) of Neisseria meningitidis B a 5.5 kb DNA fragment encodes proteins with strong homologies to enzymes of the lipopolysaccharide biosynthetic pathway of Salmonella typhimurium and Escherichia coli, GalE, RfbB, RfbC and RfbD . A meningococcal galE mutant expressed a truncated lipooligosaccharide (LOS), which terminated at the glucose residue between inner and outer core, and a second galE gene present outside the cps cluster was found to be transcriptionally and functionally inactive and, thus, unable to complement this defect . Because of the defect in the outer core, the LOS of the galE-defective meningococcal mutant was not sialylated . In contrast, carbohydrate analysis of the LOS of an rfb-defective meningococcal mutant revealed no difference from the LOS of the wild-type strain, suggesting that the rfb genes are inactive . This was supported by Northern blot analysis, which showed that expression of the rfb gene products was transcriptionally regulated . The inability of the meningococcal galE mutant, which cannot sialylate the LOS, allowed us to investigate the significance of LOS sialylation in relation to the presence of the polysialic acid capsule . Sialylated LOS, but not the polysialic acid capsule, is necessary to confer complete serum resistance on the meningococcus by inhibition of the alternative complement pathway.

FEMS Microbiol Lett, 1994 Feb 15, 116(2), 123 - 9
Genetic diversity of the iron-binding protein (Fbp) gene of the pathogenic and commensal Neisseria; Genco CA et al.; The pathogenic Neisseria and most commensal Neisseria species produce an iron-binding protein (Fbp) when grown under iron-limited conditions . In the current study, we confirmed the presence of Fbp, as well as DNA sequences homologous to the gonococcal fbp, in strains of N . gonorrhoeae, N . meningitidis, N . cinerea, N . lactamica, N . subflava, N . kochii and N . polysaccharea . The fbp genes from these strains were amplified by the polymerase chain reaction, digested with StuI or RsaI, and the restriction patterns examined . The patterns for the gonococcal and meningococcal fbp were virtually identical; however, variations were observed in the fbp sequences of the commensal Neisseria species . N . flavescens, N . mucosa, N . sicca, N . ovis and Branhamella catarrhalis, did not produce Fbp as detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and reactivity with an Fbp specific monoclonal antibody, nor did they hybridize to an fbp-specific DNA probe.

Infect Immun, 1994 Feb, 62(2), 700 - 3
Acquisition of heme iron by Neisseria meningitidis does not involve meningococcal transferrin-binding proteins; Martel N et al.; Similarities in size between hemin-binding protein 1 (HmBP1) and transferrin-binding protein 1 (TBP1) of Neisseria meningitidis suggest that these proteins are functionally homologous . However, a meningococcal mutant lacking the transferrin-binding proteins retained the capacity to acquire iron from heme and hemoglobin . In immunoblots, hyperimmune polyclonal antiserum against TBP1 did not react with HmBP1.

Curr Opin Pediatr, 1994 Feb, 6(1), 23 - 8
Epidemiology, management, and prevention of meningococcal infections; Voss L et al.; Neisseria meningitidis is the cause of significant morbidity and mortality worldwide, both in epidemic and endemic disease form . The use of serotyping, subtyping, and multilocus electrophoresis has had a significant impact on determination of the epidemiology of meningococcal disease . Recent advances in understanding the pathogenesis of meningococcal disease, include information on the role of cytokines and other inflammatory mediators, which may contribute to establishment of additional diagnostic and treatment options . Early treatment is required to improve outcome along with the use of prophylaxis to prevent secondary disease . Vaccines against groups A, C, Y, and W135, are available but have limitations, with regard to efficacy and duration of protection . Over the past decade there has been rapid progress in the development of a vaccine against group B disease, with protective trials underway in several countries . However, varying results have been found and these vaccines have not reached a stage of providing universal protection against group B meningococcal disease.

Int J Pept Protein Res, 1994 Feb, 43(2), 166 - 72
Simultaneous multiple synthesis and selective conjugation of cyclized peptides derived from a surface loop of a meningococcal class 1 outer membrane protein; Brugghe HF et al.; Starting from the alpha-(2,4-dimethoxybenzyl) ester of N-(9-fluorenylmethoxycarbonyl)aspartic acid {Fmoc-Asp-ODmb}, side-chain-protected resin-bound Fmoc-peptides containing an N epsilon-1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl lysyl {Lys(Dde)} residue were prepared . The C-terminal dimethoxybenzyl esters of aspartic acid were removed with 1% trifluoroacetic acid and 10% anisole in dichloromethane, followed by Fmoc-cleavage in the usual manner . The resin-bound peptides were then cyclized using 1-benzotriazolyloxy-tris-{N-pyrrolidino}phosphonium hexafluorophosphate (PyBOP) in the presence of N-methylmorpholine . The (dimethyldioxocyclohexylidene)ethyl groups of lysine were removed with 1% hydrazine hydrate in N,N-dimethylacetamide, and the liberated side-chain amino functions were modified by reaction with pentafluorophenyl S-acetylmercaptoacetate (SAMA-OPfp) . Finally, the peptides were side-chain deprotected, with exception of the Lys(SAMA) residue, and cleaved from the solid support with trifluoroacetic acid/anisole/water, 95/2.5/2.5 . Cyclic peptides comprising 7-14 amino acid residues were obtained employing this procedure . As a model conjugation, cyclo{Thr-Asn-Asn-Asn-Leu-Lys(SAMA)-Thr-Lys-Asp} was coupled with bromoacetamide . The same peptide was also coupled with a bromoacetylpeptide to give a well defined peptide/peptide conjugate . All peptides were conjugated to bromoacetylated tetanus toxoid for immunization purposes.

Mol Microbiol, 1994 Feb, 11(4), 725 - 37
Identification and cloning of a fur homologue from Neisseria meningitidis; Thomas CE et al.; The iron response in a number of bacterial systems is mediated by fur (ferric uptake regulation)-like regulatory systems . We have cloned and characterized a gene from Neisseria meningitidis that was homologous to Escherichia coli fur . This clone was capable of modulating expression from both E . coli and neisserial iron-regulated promoters in response to iron, and it produced a protein that reacted with anti-E . coli fur serum . Although the DNA and predicted amino acid sequences were very similar to those of four other published fur homologues, meningococcal fur was the most divergent of the group . Inability to construct a meningococcal fur mutant suggested that fur may be essential in this species.

An Med Interna, 1994 Feb, 11(2), 86 - 8
{Cavitated lung pneumonia due to meningococcus}; Arrate C et al.; Neisseria meningitidis is a common germ of the respiratory pathways which seldom produces pulmonary infection . Some established cases of pneumonia by meningococcus and, exceptionally, of complications like the empyema, have been described . However, just one case of cavitated pneumonia by N . meningitidis has been described in the medical literature . We present a case of pneumonia with cavitation produced by N . meningitidis, which was diagnosed through fibrobronchoscopy with transbronchial biopsy . This observation is of very high clinical interest, because N . meningitidis is a pathogenic agent which is not taken into account for the differential diagnosis of cavitated pneumonias.

Ann Trop Med Parasitol, 1994 Feb, 88(1), 59 - 64
Meningococcal disease in Malawi: studies on the genetic relatedness of the bacteria; Bellete B et al.; Seventy-seven meningococci, isolated from patients and carriers during a large epidemic of meningococcal meningitis in Malawi, were characterized in terms of antimicrobial susceptibility, plasmid content and multi-locus enzyme electrophoresis (MLEE) . All the isolates were sensitive to chloramphenicol but six had high enough minimum inhibitory concentrations of penicillin (> or = 2 mg/litre) to render them clinically resistant . Only one isolate was sensitive to sulphonamides but all the isolates were sensitive to rifampicin and ciprofloxacin, two drugs that would be suitable alternatives in prophylaxis . None of the isolates carried plasmids . MLEE indicated that 32 (80%) of the cerebrospinal fluid isolates and 22 (69%) of those from carriers were closely related genetically (in two electropherotypes that differed at only one allele) . The Malawian group A meningococci differed from three Ethiopian isolates by two or three alleles, indicating that direct spread from the sub-Saharan meningitis belt to Malawi was unlikely.

Acta Neurol Scand, 1994 Feb, 89(2), 139 - 42
Sequelae one year after meningococcal disease; Naess A et al.; Of 99 consecutive patients with meningococcal disease, 6 died during the acute stage . The 93 survivors were examined one year after hospitalization . 21 (40%) of the adults and 6 (15%) of the children had definite sequelae, and an additional 27% and 11% possible sequelae . 6 adults (12%) and 1 child (2%) had definite neurological sequelae . Electroencephalography (EEG) abnormalities were observed in 7 adults (14%) and 2 children (5%) . Epileptogenic activity was present in 3 of these, but none had experienced seizures . 8 adults (19%) and 5 children (14%) had sensorineural hearing loss or impaired vestibular function . Cerebral computerized tomography (CT) scan showed definite and possible abnormalities in 1 (3%) and 6 (18%), respectively, of the 34 patients tested . Neuropsychological tests were performed in 9 patients, 2 of these showed definite impairment . The frequency of neurological abnormalities was higher than in many previous studies, probably reflecting the more comprehensive examinations performed in the present study . However, only 3 patients had serious sequelae . The results suggest that the occurrence of sequelae after meningococcal disease is related to the severity of the acute disease . This may explain the higher rate of sequelae in adults, who have a higher proportion of seriously ill patients . The presence of meningitis is not required for the occurrence of neurological sequelae.

Clin Infect Dis, 1994 Feb, 18(2), 161 - 5
Increase in moderate penicillin resistance and serogroup C in meningococcal strains isolated in Spain . Is there any relationship?
Berron S, Vazquez JA.
Serogroup B Neisseria meningitidis is the main cause of meningococcal disease in Spain, but in recent years we have detected an increase in the prevalence of infection due to serogroup C meningococci . At the same time, the frequency of moderately penicillin-resistant (PenR) clinical isolates, which include greater numbers of serogroup C meningococci than do penicillin-susceptible (PenS) strains, has also been increasing . When we analyzed the prevalence of serogroups B and C in PenR and PenS meningococcal strains, we found a simultaneous increase in serogroup C strains and a decrease in serogroup B meningococci affecting both PenR and PenS isolates . To analyze this epidemiological change in Spain, we have applied serotyping, subtyping, and multilocus enzyme electrophoresis to serogroup C (PenR and PenS) strains . The two major serotypes were 2b and 2a in both groups (PenR and PenS), but our results suggested an association between serotype 2b and PenR strains . However, multilocus enzyme electrophoresis showed that 75% of the major serotypes belonged to the same electrophoretic type . It does not appear that a new clone distinct from those already established is contributing to the increase in serogroup C meningococci in Spain.

J Clin Microbiol, 1994 Feb, 32(2), 323 - 30
Asymptomatic carriage of Neisseria meningitidis in a randomly sampled population; Caugant DA et al.; To estimate the extent of meningococcal carriage in the Norwegian population and to investigate the relationship of several characteristics of the population to the carrier state, 1,500 individuals living in rural and small-town areas near Oslo were selected at random from the Norwegian National Population Registry . These persons were asked to complete a questionnaire and to volunteer for a bacteriological tonsillopharyngeal swab sampling . Sixty-three percent of the selected persons participated in the survey . Ninety-one (9.6%) of the volunteers harbored Neisseria meningitidis . The isolates were serogrouped, serotyped, tested for antibiotic resistance, and analyzed by multilocus enzyme electrophoresis . Eight (8.8%) of the 91 isolates represented clones of the two clone complexes that have been responsible for most of the systemic meningococal disease in Norway in the 1980s . Age between 15 and 24, male sex, and active and passive smoking were found to be independently associated with meningococcal carriage in logistic regression analyses . Working outside the home and having an occupation in transportation or industry also increased the risk for meningococcal carriage in individuals older than 17, when corrections for gender and smoking were made . Assuming that our sample is representative of the Norwegian population, we estimated that about 40,000 individuals in Norway are asymptomatic carriers of isolates with epidemic potential . Thus, carriage eradication among close contacts of persons with systemic disease is unlikely to have a significant impact on the overall epidemiological situation.

J Emerg Nurs, 1994 Feb, 20(1), 13 - 7
Emergency nurses' perceived knowledge and comfort levels regarding pediatric patients; Fredrickson JM et al.; OBJECTIVE: To assess emergency nurses' levels of preparation and education regarding pediatric patients, their levels of knowledge and comfort with specific medical conditions of these patients, and the need they perceive for special policies for pediatric patients . METHODS: Surveys were mailed to nurse managers and emergency nurses in six diverse counties, including Los Angeles and vicinity . Fifty-one nurse managers and 362 emergency nurses from 51 hospitals responded to the questionnaires . RESULTS: More than half of the emergency nurses had 6 or more years of experience; many had certificates, professional designations, and pediatric nursing education . Those with more pediatric education and those designated Pediatric Advanced Life Support, Certified Emergency Nurse, and Mobile Intensive Care Nurse reported the greatest comfort and knowledge with pediatric patients . The greatest discomfort and least knowledge were associated with neonatal emergencies, major trauma, child abuse or sexual abuse, sudden infant death syndrome, envenomation, psychiatric emergencies, meningococcemia, near-drowning, respiratory arrest, and cardiac arrest . Opinions regarding the need for special pediatric policies differed in some cases from current practice . CONCLUSION: Pediatric medical conditions associated with high nurse discomfort and low knowledge point to areas of need for specific education.

Nippon Rinsho, 1994 Feb, 52(2), 400 - 5
{Mechanisms of the intractability of bacterial infections in immunodeficiency status in childhood}; Yata J; Most of the primary immunodeficiency diseases develop in childhood . The patients with antibody deficiency are susceptible to pyogenic bacteria since antibody is essential to opsonize bacteria . T cell deficiency causes defect of cytokine production needed to activate macrophages to kill intracellular bacteria such as mycobacteria and leeds to intractable infection of such bacteria . Complement mediated bacteriolysis is important to protect neisseria such as meningococcus and deficiency of C5-C9 provides susceptibility to the bacteria . Defect of superoxide synthesis or adhesion of neutrophils is related to severe infection of pyogenic bacteria . On the way of development of immune system, children especially in early infancy display susceptibility to bacterial infections.

Nippon Rinsho, 1994 Feb, 52(2), 367 - 71
{Gram-negative coccus infection}; Matsumoto K et al.; The main pathogens of gram-negative infections are Neisseria gonorrhoeae, Neisseria meningitidis and Moraxella catarrhalis infection . N . Gonorrhoeae infection is one of the STD, but the chemotherapy for this infection is very easy because this pathogen is very susceptible to new quinolones . Meningococcal infection is very rare in Japan . Since 1980, M . catarrhalis is one of the important pathogen of respiratory infections such as acute bronchitis, pneumonia, chronic bronchitis . This pathogen also causes acute sinusitis and otitis . Most pathogenic strains of M . catarrhalis are beta-lactamase producing.

Epidemiol Infect, 1994 Feb, 112(1), 115 - 24
Patient and strain characteristics in relation to the outcome of meningococcal disease: a multivariate analysis; Scholten RJ et al.; To investigate the joint association of patient and strain characteristics with the outcome of meningococcal disease (MD), data were collected on 563 consecutive cases of MD reported between 1989 and 1990 in The Netherlands . The meningococcal isolates were characterized with regard to their surface characteristics . Sequelae occurred in 8.5% of the patients, and were only associated with the presence of bacteraemia . The case-fatality rate was 7.7% . Infants aged < or = 5 months and patients in the age-groups of 10-19 years and > or = 50 years had an increased risk for a fatal outcome compared with children from 6 months to 9 years old (Odds Ratios {ORs}: 5.1, 3.4 and 9.8, respectively) . The OR for females versus males was 2.3 . The ORs for patients with bacteraemia, or a combination of bacteraemia and meningitis, compared with meningitic patients, were 2.3 and 3.1 . Meningococcal strain characteristics did not influence the case-fatality rate substantially . In conclusion, host factors were found to be determinants for a fatal outcome of MD in The Netherlands from 1989 to 1990.

J Infect Dis, 1994 Feb, 169(2), 438 - 41
Prevalence of Neisseria meningitidis relatively resistant to penicillin in the United States, 1991 . Meningococcal Disease Study Group; Jackson LA et al.; To estimate the prevalence of Neisseria meningitidis relatively resistant to penicillin in the United States, antimicrobial susceptibility testing was performed on all US meningococcal isolates submitted to the Centers for Disease Control and Prevention in 1991, including isolates identified through population-based surveillance for invasive meningococcal disease in selected areas of the United States . Three of the 100 isolates tested had MICs of penicillin of 0.125 microgram/mL . All were serogroup B, beta-lactamase-negative, and unique by multilocus enzyme electrophoresis subtyping . None of the 3 patients had been treated solely with penicillin; all recovered completely . About 4% of the isolates obtained from the population-based surveillance system were relatively penicillin-resistant . Given the low prevalence and uncertain clinical significance of infection with these organisms, routine susceptibility testing of meningococcal isolates is not indicated at this time; however, continued surveillance is necessary to monitor trends in antimicrobial susceptibility of meningococci in the United States.

Eur J Clin Microbiol Infect Dis, 1994 Feb, 13(2), 174 - 7
Characteristics of serogroup A Neisseria meningitidis strains isolated in the Central African Republic in February 1992; Guibourdenche M et al.; A severe epidemic of serogroup A meningococcus meningitis occurred in the northwest Central African Republic from January to March 1992 . Strains from 24 patients were characterized using serotyping, testing of susceptibility to antibiotics, and multilocus enzyme electrophoresis . In 23 of the 24 patients the causal strain was found to be 4:P1.9/clone III-1 . These results indicate that such strains continue to spread in Africa and have taken hold in areas outside the "meningitis belt." This may be a consequence of changing climatic conditions.

Microb Pathog, 1994 Feb, 16(2), 153 - 63
Interactions of Neisseria meningitidis with human monocytes; McNeil G et al.; The roles of capsule, pili and Class 5 outer-membrane proteins (Opa and Opc) of Neisseria meningitidis (Nm) in bacterial interactions with human monocytes were investigated using several meningococcal isolates of different serogroups . The presence of either Class I or Class II pili in capsulate strains of several serogroups had no significant effect on adherence to and internalisation by monocytes . Using clonal variants derived from a non-piliated serogroup A strain, C751, it was observed that capsulate bacteria (cap+) failed to interact with human monocytes in significant numbers whether or not they expressed outer-membrane proteins . These bacteria were also resistant to phagocytic killing . For capsule-deficient bacteria, expression of the Opc protein or OpaBC751 correlated with high levels of association, while the expression of OpaDC751 or OpaAC751 resulted in comparatively lower levels . Bacteria expressing undetectable levels of Opc or Opa proteins (Opc-, Opa-) failed to interact with monocytes . In phagocytic killing assays, Opc-expressing bacteria (Opc+) as well as Opa-expressing bacteria (Opa+) were killed more readily than Opc-, Opa- bacteria (30% decrease in viability of Opc+ bacteria; 18%, 10% and 8% decrease in viability of OpaB+, OpaD+ and OpaA+ bacteria) . A study of intracellular survival showed a gradual decrease in viability of both capsulate and capsule-deficient bacteria . However, proportionately greater numbers of capsule-deficient bacteria were internalized and consequently larger numbers survived over a 4-h period . Prolonged bacterial survival within phagocytic cells may have implications in dissemination of bacteria by carriage within these cells.

J Bacteriol, 1994 Jan, 176(2), 333 - 7
Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N . meningitidis: natural events and laboratory simulation; Bowler LD et al.; The penicillin-binding protein 2 genes (penA) of penicillin-resistant Neisseria meningitidis have a mosaic structure that has arisen by the introduction of regions from the penA genes of Neisseria flavescens or Neisseria cinerea . Chromosomal DNA from both N . cinerea and N . flavescens could transform a penicillin-susceptible isolate of N . meningitidis to increased resistance to penicillin . With N . flavescens DNA, transformation to resistance was accompanied by the introduction of the N . flavescens penA gene, providing a laboratory demonstration of the interspecies recombinational events that we believe underlie the development of penicillin resistance in many meningococci in nature . Surprisingly, with N . cinerea DNA, the penicillin-resistant transformants did not obtain the N . cinerea penA gene . However, the region of the penA gene derived from N . cinerea in N . meningitidis K196 contained an extra codon (Asp-345A) which was not found in any of the four N . cinerea isolates that we examined and which is known to result in a decrease in the affinity of PBP 2 in gonococci.

J Infect Dis, 1994 Jan, 169(1), 157 - 61
Differential expression of proinflammatory cytokines and their inhibitors during the course of meningococcal infections; van Deuren M et al.; Circulating concentrations of tumor necrosis factor-alpha (TNF), interleukin (IL)-1 beta, IL-6, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptors p55 (sTNFr-55) and p75 (sTNFr-75) and ex vivo production of TNF, IL-1, IL-6, and IL-1ra using a whole blood culture system were measured during the acute and convalescent stages of meningococcal infection . Circulating TNF and IL-1 were below detection level, whereas IL-6 and IL-1ra, sTNFr-55, and sTNFr-75 were increased at admission . The ex vivo production of proinflammatory cytokines TNF, IL-1, and IL-6 was suppressed at admission and restored gradually during recovery . On the contrary, the production of the antiinflammatory IL-1ra was increased at admission . The elevated concentrations of both IL-1ra and sTNFr early in the course of infection suggest a regulatory role for these antiinflammatory compounds . The observed down-regulation of the ex vivo production of TNF, IL-1, and IL-6 and up-regulation of the production of IL-1ra in the acute stage may indicate a protective regulation mechanism.

CMAJ, 1994 Jan 1, 150(1), 29 - 35
Role of whole-cell pertussis vaccine in severe local reactions to the preschool (fifth) dose of diphtheria-pertussis-tetanus vaccine; Scheifele DW et al.; OBJECTIVE: To estimate the contribution of whole-cell pertussis vaccine to severe local reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine . DESIGN: Double-blind randomized controlled trial . SETTING: Urban community . PARTICIPANTS: Volunteer sample of 200 healthy children 4 to 6 years old who were eligible for the fifth dose of DPT vaccine . INTERVENTIONS: Children received, in both arms, either diphtheria toxoid-tetanus toxoid (DT) and monovalent pertussis vaccines (group A, 99 children) or DPT and meningococcal vaccines (group B, 101 children) . All were licensed products from single lots . The children were assessed 24 hours later by a trained observer . Serum samples obtained before vaccination were tested for antibodies to tetanus and diphtheria toxins and five pertussis antigens by means of enzyme-linked immunosorbent assay . MAIN OUTCOME MEASURES: Rates of severe local reactions (an area of redness or swelling or both of 50 mm or greater) 24 hours after vaccination . Relation between serum antibody levels before vaccination and rates of severe local reactions to corresponding vaccines . RESULTS: All of the subjects were followed up 24 hours after vaccination . Severe redness was present in 38% given DPT vaccine, 29% given intramuscular pertussis vaccine and 9% given DT vaccine (p < or = 0.002, three-way comparison) . Severe swelling was common after vaccination with all three products . After intramuscular pertussis vaccination a relation was evident between the prevaccination levels of antibody to whole-cell pertussis bacteria and the rates of redness (p < 0.02) but not between the prevaccination subcellular antibody levels and the rates of redness . CONCLUSION: That pertussis vaccine resembled the DPT vaccine in causing severe redness suggests that it is the principal cause of such reactions after DPT vaccination . The DT vaccine was also reactogenic; thus, cumulative sensitization to one or more of its constituents may be a factor.

Zh Mikrobiol Epidemiol Immunobiol, 1994 Jan-Feb, (1), 51 - 5
{The activity of natural killers and K cells and their interferon sensitivity in subjects inoculated against diphtheria and meningococcal infection}; Pchelintsev SIu et al.; The work deals with the time course of changes in the activity of natural killers, K-cells, their sensitivity to interferon, which reflects, in our opinion, the reserve possibilities of this killer system simultaneously with the development of the specific sensitization of lymphocytes . Significant changes in the cytotoxicity of natural killers, K-cells, have been detected in persons immunized against meningococcal infection, especially in those immunized with meningococcal vaccine introduced in combination with diphtheria toxoid . In this latter group of volunteers even more pronounced sensitization of peripheral blood lymphocytes has been observed than in persons immunized with monopreparations . The results obtained in this investigation indicate that the determination of these cell reactions may be of importance in the evaluation of the effectiveness of immunization.

Br J Clin Pract, 1994 Jan-Feb, 48(1), 27 - 8
Primary meningococcal conjunctivitis in children; Neoh C et al.; Four cases of primary meningococcal conjunctivitis in children are reported . This represents an incidence of 2% of patients presenting with conjunctivitis to a paediatric A&E department . All were initially treated with topical chloramphenicol, followed by systemic rifampicin once the diagnosis had been established . No ocular or systemic complications developed, nor recolonisation of the conjunctiva or colonisation of the nasopharynx at follow-up (1-2 years).

J Infect, 1994 Jan, 28(1), 73 - 5
Meningococcaemia: a life threatening complication of upper gastrointestinal endoscopy; al-Zamil F et al.; Minor and major complications of diagnostic and therapeutic upper gastrointestinal endoscopy, especially after injection sclerotherapy, are well recognised . We report a case of septicaemia with Neisseria meningitidis serogroup A in a 4-year-old girl after diagnostic endoscopy.

Mol Microbiol, 1994 Jan, 11(1), 15 - 22
Clonal spread of serogroup A meningococci: a paradigm for the analysis of microevolution in bacteria; Achtman M; Extensive epidemiological analyses of epidemics of meningococcal meningitis have resulted in large, well-defined strain collections which represent the local diversity and global spread of serogroup A bacteria . Several genes for cell surface proteins are conserved during spread, with a few exceptions: analysis of these exceptions has revealed some of the phenomena which can lead to microevolution . Microevolution is so rapid with serogroup A meningococci that several independent recombination events have been documented within the last few decades . In a few cases, the recombinant bacteria have become established by clonal replacement plus epidemic spread . Comparison with other bacteria indicates that serogroup A meningococci provide a number of advantages for analysis of microevolution.

Klin Lab Diagn, 1994, (1), 47 - 50
{Bacterioscopy of cerebrospinal fluid from patients with generalized forms of meningococcal infection}; Il'ina TV; The author analyzes the potentialities of bacterioscopic examinations of cerebrospinal fluid samples of patients with meningococcal infection and correlations of the liquor appearance characteristics and bacteriologic data . The findings are extremely important for practical laboratories, for they permit an adequate assessment of bacteriologic examinations and improve their quality . Six CSF groups may be distinguished, differing in their type . A relationship has been revealed between liquor appearance and bacteriologic and bacterioscopic findings, this relationship being prognostically and diagnostically significant.

Ann Trop Paediatr, 1994, 14(4), 275 - 9
Reactogenicity and safety of meningococcal A and C vaccine in Saudi children; al-Eissa YA; During an outbreak caused by group A Neisseria meningitidis in March 1992, groups A and C meningococcal polysaccharide vaccine was administered to 1,168 children aged from 2 to 18 years . Parents were surveyed to ascertain reactions of children to the vaccine and development of invasive group A meningococcal disease after immunization . The most common reactions were mild local pain (21.9%), erythema (12.2%), and swelling at the injection site (7.2%) . Only 1.7% of the children experienced fever and 3.7% displayed irritability . The vaccine was well tolerated and all adverse reactions disappeared within 24-48 hours of immunization . No cases of meningitis or sepsis caused by group A meningococci were seen in the 1st 12 months of observation among the vaccinated children.

Scand J Infect Dis, 1994, 26(6), 771 - 3
Group B meningococcal meningitis in India; Suri M et al.; The first case of infection with Group B meningococcus in India is reported . The patient was a 4-month-old boy who presented with meningitis and died within 6 h of admission . Gram stain of CSF showed meningococci and latex particle agglutination test on CSF was strongly positive for Neisseria meningitidis serogroup B . The CSF was also positive for meningococcus by polymerase chain reaction using primers NM1 and NM6, which amplify a 650 bp region of the dihydropteroate synthase (dhps) gene of N . meningitidis.

Scand J Infect Dis, 1994, 26(6), 719 - 23
Parental smoking and carriage of Neisseria meningitidis among Greek schoolchildren; Kremastinou J et al.; In December 1990 and January 1991, primary (320) and secondary (697) pupils in 2 areas of Athens were screened to determine the rate of carriage of Neisseria meningitidis and to determine if the genetic and environmental factors associated with carriage of meningococci in Greece were similar to those observed for northern European populations . In 1 area, socioeconomic indicators were significantly lower than in the other (p < 0.0005), but the isolation rates from pupils in the areas were similar, 5.3% and 6.3% . In contrast to studies in northwest Europe, carriage was not associated with lower socioeconomic conditions, sex, numbers of individuals per household, upper respiratory tract infection, or secretor status . By univariate analysis, carriage was associated with age (15-18 years) (p < 0.05) and mother's or other carer's smoking habits (p < 0.05)--but not father's smoking . Although the proportion of fathers who smoked was greater in the area where socioeconomic indicators were lower (61%) vs . (47%) (p < 0.0005), the proportions of women smokers were similar (33% vs . 38%) . By multiple regression analysis, the only significant factors were age (p < 0.01) and carer's smoking (p < 0.05).

Medicina (B Aires), 1994, 54(5 Pt 1), 427 - 30
{Failure of the treatment with penicillin in a case of Neisseria meningitidis meningitis}; Bardi L et al.; Most Neisseria meningitidis are susceptible to penicillin with a minimal inhibitory concentration (MIC) < or = 0.6 mg/L and mortality related to meningococcal meningitis has been low . In recent years, however, N . meningitidis moderately susceptible to penicillin (MIC 0.12-1 mg/L) has been isolated in South Africa, England, USA, and mainly Spain . We report a case of a 16-year old male patient, who was admitted with a diagnosis of meningitis . Because group C N . meningitidis was isolated from cerebrospinal fluid, the patient received 300,000 Ul/Kg penicillin G . Seventy-two hours later, a new lumbar puncture was performed, and N . meningitidis was again isolated from culture . Beta-lactamase activity of the isolate was negative and MIC measurement showed that it was moderately susceptible to penicillin, probably due to modification of a penicillin binding protein . Penicillin G was then discontinued, and the patient was given 50 mg/Kg ceftriaxone . A third lumbar puncture performed on the eighth day after admission showed a negative bacteriological culture . The patient was discharged without neurological sequelae after 14 days of treatment . This case report shows that small changes in N . meningitidis sensitivity may be of clinical relevance.

Mol Microbiol, 1994 Jan, 11(1), 175 - 87
Immunogenicity and evolutionary variability of epitopes within IgA1 protease from serogroup A Neisseria meningitidis; Morelli G et al.; Five murine epitopes were defined and mapped within IgA1 protease produced by Neisseria meningitidis . Epitopes 1 and 2 were present in IgA1 protease from all strains, and from Neisseria gonorrhoeae . Epitopes 3 through to 5 varied between subgroups of serogroup A meningococci, but have remained constant over decades within the subgroups, except for epitope 4, which changed between 1983 and 1987 during the spread of subgroup III meningococci from Asia to Africa . Binding of monoclonal antibodies to epitopes 1, 4 and 5 neutralized enzymatic function . Human sera containing antibodies to IgA1 protease as a result of natural infection inhibited binding of monoclonal antibodies to epitope 4 but not to the other epitopes.

J Clin Microbiol, 1993 Dec, 31(12), 3255 - 9
E test as susceptibility test and epidemiologic tool for evaluation of Neisseria meningitidis isolates; Hughes JH et al.; The E test (AB Biodisk, Solna, Sweden), a new approach developed to test antimicrobial susceptibility, was compared with the agar dilution method for seven-drug antibiogram analysis of Neisseria meningitidis isolates . The overall E-test quantitative accuracy (+/- 1 log2 dilution) was 93% compared with that of agar dilution testing . The E test was then used to perform the susceptibility tests on a 10-year sample of 102 N . meningitidis isolates, including 5 from a recent epidemic outbreak in the University of Iowa (Iowa City) community . The E test proved to be an efficient methodology for identifying common source clusters of meningococcal disease having resistance to rifampin or sulfonamides . Moreover, the data demonstrated a recent increase in penicillin MICs (MIC for 90% of strains, 0.094 microgram/ml) and an escalation of high-level resistance to trimethoprimsulfamethoxazole (33%) and rifampin (14%) . The E test should be considered a simple and accurate susceptibility method for the emerging need to test meningococci and other pathogenic neisserias . Chocolate Mueller-Hinton agar was observed to provide the best support of growth and E-test MIC results that correlated well with results of the reference agar dilution method previously used for neisserias.

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