PubMed Health⌕ Search

Biomedical subjects

D S Stephens

Publications and source records attributed to D S Stephens.

At least 37 records · Page 2Linked to original sources
PubMed1999

Maternal cigarette smoking and invasive meningococcal disease: a cohort study among young children in metropolitan Atlanta, 1989-1996.

OBJECTIVES: This study assessed the association between maternal cigarette smoking during pregnancy and the risk of invasive meningococcal disease during early childhood. METHODS: Using a retrospective cohort study design, cases from an active surveillance project monitoring all invasive meningococcal disease in the metropolitan Atlanta area from 1989 to 1995 were merged with linked birth and death certificate data files. Children who had not died or acquired meningococcal disease were assumed to be alive and free of the illness. The Cox proportional hazards analysis was used to assess the independent association between maternal smoking and meningococcal disease. RESULTS: The crude rate of meningococcal disease was 5 times higher for children whose mothers smoked during pregnancy than for children whose mothers did not smoke (0.05% vs 0.01%). Multivariate analysis revealed that maternal smoking (risk ratio [RR] = 2.9; 95% confidence interval [CI] = 1.5, 5.7) and a mother's having fewer than 12 years of education (RR = 2.1; 95% CI = 1.0, 4.2) were independently associated with invasive meningococcal disease. CONCLUSIONS: Maternal smoking, a likely surrogate for tobacco smoke exposure following delivery, appears to be a modifiable risk factor for sporadic meningococcal disease in young children.

Adult↗
PubMed1998

The lipooligosaccharide (LOS) of Neisseria meningitidis serogroup B strain NMB contains L2, L3, and novel oligosaccharides, and lacks the lipid-A 4'-phosphate substituent.

The complete structure of the lipooligosaccharide (LOS) from Neisseria meningitidis strain NMB (serotype 2b:P1.2,5), a serogroup B cerebrospinal fluid isolate, was determined. Two oligosaccharide (OS) fractions and lipid-A were obtained following mild acid hydrolysis of the LOS. The structures in these fractions were determined using glycosyl composition and linkage analyses, N spectroscopy and mass spectrometry. One oligosaccharide fraction (OS1) consists of a molecule having a glycosyl sequence identical to that previously reported for the LOS from immunotype L2 N. meningitidis [A. Gamain, M. Beurret, F. Michon, J.-R. Brisson, and H.J. Jennings, J. Biol. Chem.,267,(112) 922-925] i.e., a lacto-N-neotetraose is attached to heptose I (Hep I), with terminally linked N-acetylglucosaminosyl and glucosyl residues attached to Hep II of the inner core. Approximately 70% of this structure is acetylated at O-6 of the terminally linked alpha-N-acetyl-glucosaminosyl residue. As with the L2 structure, the NMB LOS contained phosphoethanolamine (PEA) at O-6 or O-7 of the Hep II residue. The second oligosaccharide fraction (OS2) contains a a mixture of three different molecules, all of which vary from one another in their glycosyl substitution patterns of the Hep II residue. The most abundant molecule in OS2 has a structure identical to that of OSI, i.e., it has the L2 glycosyl sequence. A second molecule (OS2a) lacks the terminal glucosyl residue at O-3 of Hep II; i.e., it has a glycosyl sequence identical to that of the mild acid released oligosaccharide of N. meningitidis immunotype L3, L4, or L7 LOSs. The third molecule (OS2b) is a novel structure that lacks the terminal N-acetylglucosaminosyl residue linked to O-2 of Hep II. Overall, 76% of OS released from NMB LOS has the L2 structure, 15% is OS2a (L3), and 9% is OS2b. A portion (20%) of the molecules in the NMB LOS preparation also contained terminally linked sialic acid attached to O-3 of the lacto-N-neotetraose galactosyl residue, which is also consistent with the L3, or L4 LOS structures. In contrast to the previously reported structure of N. meningitidis lipid-A [V. A. Kulshin, U. Zähringer, B. Linder, C.E. Frasch, C-M. Tsai, B.A. Dmitriev, and E.T Rietschel, J. Bacteriol., 174, (1992)1793-1800], only 30% of the lipid-A from NMB LOS possesses 4'-phosphate. Comparison with the lipid-A of LOS purified from an isogenic acapsulate mutant, M7, revealed that the 4'-position was almost completely occupied with phosphate. These data emphasize the structural heterogeneity of the OS and phosphate substituents of Hep II, and 4'-phosphorylation of lipid-A of meningococcal LOS.

Carbohydrate Sequence↗
PubMed1998

Genetic basis for biosynthesis, structure, and function of meningococcal lipooligosaccharide (endotoxin).

The exclusive human pathogen Neisseria meningitidis expresses lipooligosaccharide (LOS), an endotoxin that is structurally distinct from the lipopolysaccharides (LPS) of enteric Gram-negative bacilli. Differences that appear to be biologically important occur in the composition and attachment of acyl chains to lipid A, phosphorylation patterns of lipid A, and the incorporation and phosphorylation of sugar residues in the LOS inner core. Further, unlike most enteric LPS, only two to five sugar residues are attached to the meningococcal LOS inner core, and there are no multiple repeating units of O-antigens. In contrast to Escherichia coli, where the LPS biosynthesis genes are organized as large operons, the meningococcal LOS biosynthesis genes are organized into small operons or are located individually in the chromosome. Some of these genetic loci in meningococci and gonococci display polymorphisms caused by localized chromosomal rearrangements. One mechanism of antigenic variation of meningococci LOS is the regulation of glycosyltransferase activity by slipped strand mispairing of homopolymeric tracts within the 5' end of the genes encoding these enzymes, resulting in the addition of different sugar residues to the LOS molecule. Meningococcal LOS is a critical virulence factor in N. meningitidis infections and is involved in many aspects of pathogenesis, including the colonization of the human nasopharynx, survival after bloodstream invasion, and the inflammation associated with the morbidity and mortality of meningococcemia and meningitis. Meningococcal LOS, which is a component of serogroup B meningococcal vaccines currently in clinical trials, has been proposed as a candidate for a new generation of meningococcal vaccines. The rapidly expanding knowledge of the genetic basis for biosynthesis, structure, and regulation of meningococcal LOS provides insights into unique endotoxin structures and the precise role of LOS in the pathogenesis of meningococcal disease.

Bacterial Vaccines↗
PubMed1998

Emerging and reemerging infectious diseases: a multidisciplinary perspective.

Predictions that infectious diseases would be eliminated as a major threat to human health have been shattered by emerging and reemerging infections, among them acquired immunodeficiency syndrome (AIDS), hemorrhagic fevers, marked increases in infections caused by antimicrobial-resistant bacteria, and the resurgence of tuberculosis and malaria. Understanding the dynamics of emerging and reemerging infections is critical to efforts to reduce the morbidity and mortality of such infections, to establish policy related to preparedness for infectious threats, and for decisions on where to use limited resources in the fight against infections. In order to offer a multidisciplinary perspective, 23 infectious disease specialists, epidemiologists, geneticists, microbiologists, and population biologists participated in an open forum at Emory University on emerging and reemerging infectious diseases. As summarized below, the group addressed questions about the definition, the identification, the factors responsible for, and multidisciplinary approaches to emerging and reemerging infections.

Acquired Immunodeficiency Syndrome↗
PubMed1998

The (alpha2-->8)-linked polysialic acid capsule and lipooligosaccharide structure both contribute to the ability of serogroup B Neisseria meningitidis to resist the bactericidal activity of normal human serum.

The molecular basis for the resistance of serogroup B Neisseria meningitidis to the bactericidal activity of normal human sera (NHS) was examined with a NHS-resistant, invasive serogroup B meningococcal isolate and genetically and structurally defined capsule-, lipooligosaccharide (LOS)-, and sialylation-altered mutants of the wild-type strain. Expression of the (alpha2-->8)-linked polysialic acid serogroup B capsule was essential for meningococcal resistance to NHS. The very NHS-sensitive phenotype of acapsular mutants (99.9 to 100% killed in 10, 25, and 50% NHS) was not rescued by complete LOS sialylation or changes in LOS structure. However, expression of the capsule was necessary but not sufficient for a fully NHS-resistant phenotype. In an encapsulated background, loss of LOS sialylation by interrupting the alpha2,3 sialyltransferase gene, lst, increased sensitivity to 50% NHS. In contrast, replacement of the lacto-N-neotetraose alpha-chain (Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) with glucose extensions (GlcN) in a galE mutant resulted in a strain resistant to killing by 50% NHS at all time points. Encapsulated meningococci expressing a Hep2(GlcNAc)-->KDO2-->lipid A LOS without an alpha-chain demonstrated enhanced sensitivity to 50% NHS (98% killed at 30 min) mediated through the antibody-dependent classical complement pathway. Encapsulated LOS mutants expressing truncated Hep2-->KDO2-->lipid A and KDO2-->lipid A structures were also sensitive to 50% NHS (98 to 100% killed at 30 min) but, unlike the wild-type strain and mutants with larger oligosaccharide structures, they were killed by hypogammaglobulinemic sera. These data indicate that encapsulation is essential but that the LOS structure contributes to the ability of serogroup B N. meningitidis to resist the bactericidal activity of NHS.

Bacterial Capsules↗
PubMed1998

Characterization of the gene cassette required for biosynthesis of the (alpha1-->6)-linked N-acetyl-D-mannosamine-1-phosphate capsule of serogroup A Neisseria meningitidis.

The (alpha1-->6)-linked N-acetyl-D-mannosamine-1-phosphate meningococcal capsule of serogroup A Neisseria meningitidis is biochemically distinct from the sialic acid-containing capsules produced by other disease-associated meningococcal serogroups (e.g., B, C, Y, and W-135). We defined the genetic cassette responsible for expression of the serogroup A capsule. The cassette comprised a 4,701-bp nucleotide sequence located between the outer membrane capsule transporter gene, ctrA, and galE, encoding the UDP-glucose-4-epimerase. Four open reading frames (ORFs) not found in the genomes of the other meningococcal serogroups were identified. The first serogroup A ORF was separated from ctrA by a 218-bp intergenic region. Reverse transcriptase (RT) PCR and primer extension studies of serogroup A mRNA showed that all four ORFs were cotranscribed in the opposite orientation to ctrA and that transcription of the ORFs was initiated from the intergenic region by a sigma-70-type promoter that overlapped the ctrA promoter. The first ORF exhibited 58% amino acid identity with the UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) 2-epimerase of Escherichia coli, which is responsible for the conversion of UDP-GlcNAc into UDP-N-acetyl-D-mannosamine. Polar or nonpolar mutagenesis of each of the ORFs resulted in an abrogation of serogroup A capsule production as determined by colony immunoblots and enzyme-linked immunosorbent assay. Replacement of the serogroup A biosynthetic gene cassette with a serogroup B cassette by transformation resulted in capsule switching from a serogroup A capsule to a serogroup B capsule. These data indicate that assembly of the serogroup A capsule likely begins with monomeric UDP-GlcNAc and requires proteins encoded by three other genes found in the serogroup A N. meningitidis-specific operon located between ctrA and galE.

Bacterial Capsules↗
PubMed1997

Capsule switching of Neisseria meningitidis.

The different sialic acid (serogroups B, C, Y, and W-135) and nonsialic acid (serogroup A) capsular polysaccharides expressed by Neisseria meningitidis are major virulence factors and are used as epidemiologic markers and vaccine targets. However, the identification of meningococcal isolates with similar genetic markers but expressing different capsular polysaccharides suggests that meningococcal clones can switch the type of capsule they express. We identified, except for capsule, isogenic serogroups B [(alpha2-->8)-linked polysialic acid] and C [(alpha2-->9)-linked polysialic acid] meningococcal isolates from an outbreak of meningococcal disease in the U. S. Pacific Northwest. We used these isolates and prototype serogroup A, B, C, Y, and W-135 strains to define the capsular biosynthetic and transport operons of the major meningococcal serogroups and to show that switching from the B to C capsule in the outbreak strain was the result of allelic exchange of the polysialyltransferase. Capsule switching was probably the result of transformation and horizontal DNA exchange in vivo of a serogroup C capsule biosynthetic operon. These findings indicate that closely related virulent meningococcal clones may not be recognized by traditional serogroup-based surveillance and can escape vaccine-induced or natural protective immunity by capsule switching. Capsule switching may be an important virulence mechanism of meningococci and other encapsulated bacterial pathogens. As vaccine development progresses and broader immunization with capsular polysaccharide conjugate vaccines becomes a reality, the ability to switch capsular types may have important implications for the impact of these vaccines.

Bacterial Capsules↗
PubMed1997

Molecular epidemiology of sporadic (endemic) serogroup C meningococcal disease.

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

Adolescent↗
PubMed1997

Urinary tract infection: an overview.

Urinary tract infection (UTI) remains very common. As many as 50% of women report having had at least one UTI in their lifetimes. Urinary tract infection is the most common cause of infection in nursing home residents and the most common source of bacteremia in the elderly population. Urinary tract infection occurs in patients with structurally or functionally abnormal urinary tracts (complicated UTI) and in patients with anatomically normal urinary tracts (uncomplicated UTI). Escherichia coli (E coli) is the most common cause of uncomplicated UTI, whereas antibiotic-resistant Enterobacteriaceae, enterococci, and Candida species often are the causes of complicated UTI. In this article we review current concepts of the epidemiology, microbiology, pathophysiology, clinical manifestations, diagnosis, and treatment of urinary tract infection.

Anti-Bacterial Agents↗
PubMed1996

Invasive group B streptococcal disease: the emergence of serotype V.

Group B streptococci (GBS) cause invasive disease in neonates, pregnant adults, and nonpregnant adults with underlying or chronic disease. Previous studies found capsular serotypes Ia, Ib, II, and III cause invasive disease. Prospective population-based surveillance of invasive GBS disease was done from June 1992 to June 1993 in metropolitan Atlanta: 279 patients had invasive disease. Of these, 43% were < or = 6 months old, and 57% were adults. The incidence among all adults was 7.7/100,000/year, 33% higher than in 1989-1990 (P < .01). The incidence in nonpregnant adults was 5.9/100,000/year, 37% higher than in 1989-1990 (P < .02). Serotyping of 178 patient isolates revealed that 34% had GBS serotype Ia or Ia/c, 8% had Ib/c, 6% had II or II/c, 29% had III, 0% had IV, 21% had V, and 2% were nontypeable. Serotype V was recovered from all groups and was the most common serotype from nonpregnant adults. Serotype V isolates appeared to be highly related genetically. The increasing incidence of GBS disease in adults, the changing distribution of serotypes, and the emergence of serotype V will impact vaccine strategies.

Adolescent↗
PubMed1996

The (alpha2-->8)-linked polysialic acid capsule of group B Neisseria meningitidis modifies multiple steps during interaction with human macrophages.

Group B Neisseria meningitidis causes systemic disease, including meningitis, after initial colonization and subsequent penetration of nasopharyngeal mucosa, a tissue which is richly populated by macrophages. In an initial effort to characterize the interaction of N. meningitidis and mature human macrophages, the influence of the alpha2-->8) -linked polysialic acid capsule on the interaction of N. meningitidis with human monocyte-derived macrophages was investigated with a capsulate case isolate and an isogenic Tn916-derived noncapsulate transformant. The capsulate strain was fourfold less adherent to the macrophage surface after cold incubation, although adherence of both strains was significantly increased after opsonization with nonimmune C5-depleted serum. When opsonized inocula were adjusted so that they adhered to macrophages in equal numbers, the two strains were internalized at equivalent rates and both entered membrane-bound compartments (phagosomes). Colocalization of bacteria with the late endosomal and lysosomal marker lysosome-associated membrane protein revealed that fusion of lysosomes with phagosomes containing the capsulate organism was significantly reduced 10 and 30 min after entry, but by 1 h, no difference between the strains was observed. Once internalized, meningococci were effectively killed, although more rapid killing of the capsulate strain was observed over the first 3 h. These results indicate that the (alpha2-->8)-linked polysialic acid capsule modifies the interaction of meningococci with human macrophages at multiple steps, including adherence to the macrophage surface and phagosome-lysosome fusion. Moreover, the discordance between the kinetics of phagosome- lysosome fusion and bacterial killing suggests that a nonlysosomal mechanism may be responsible for a significant fraction of macrophage killing of N. meningitidis.

Antigens, CD↗
PubMed1996

Expression of sialic acid and polysialic acid in serogroup B Neisseria meningitidis: divergent transcription of biosynthesis and transport operons through a common promoter region.

We studied capsule-defective (Cap-) serogroup B meningococcal mutants created through Tn916 or omega-fragment mutagenesis. The Cap- phenotypes were the results of insertions in three of four linked genes (synX, synC, and synD) involved in CMP-N-acetylneuraminic acid and polysialic acid capsule biosynthesis, and in ctrA the first of four linked genes involved in capsule membrane transport. Mutations in the CMP-N-acetylneuraminic acid biosynthesis genes synX and synC caused defects in lipooligosaccharide sialylation but not mutations in the putative (alpha2 -> 8)-linked polysialyltransferase (synD) or in ctrA. Reverse transcriptase PCR studies indicated that the four biosynthesis genes (synX to -D) and the capsule transport genes (ctr to -D) were separately transcribed as operons. The operons were separated by a 134-bp intergenic region. Primer extension of synX and ctrA demonstrated that transcription of the operons was divergently initiated from adjacent start sites present in the intergenic region. Both transcriptional start sites were preceded by a perfect -10 Pribnow promoter binding region. The synX to -D, but not the ctrA to -D, transcriptional start site was preceded by a sequence bearing strong homology to the consensus sigma 70 -35 promoter binding sequence. Both promoters showed transcriptional activity when cloned behind a lacZ reporter gene in Escherichia coli. Our results confirm the intrinsic relationship between polysialic acid capsule biosynthesis and lipooligosaccharide sialylation pathways in group B Neisseria meningitidis. Our study also suggests that the intergenic region separating the synX to -D and ctrA to -D operons is an important control point for the regulation of group B capsule expression through coordinated transcriptional regulation of the synX to -D and drA to -D promoters.

Bacterial Capsules↗
PubMed1996

Two glycosyltransferase genes, lgtF and rfaK, constitute the lipooligosaccharide ice (inner core extension) biosynthesis operon of Neisseria meningitidis.

We have characterized an operon required for inner-core biosynthesis of the lipooligosaccharide (LOS) of Neisseria meningitidis. Using Tn916 mutagenesis, we recently identified the alpha-1,2-N-acetylglucosamine (GlcNAc) transferase gene (rfaK), which when inactivated prevents the addition of GlcNAc and alpha chain to the meningococcal LOS inner core (C. M. Kahler, R. W. Carlson, M. M. Rahman, L. E. Martin, and D. S. Stephens, J. Bacteriol. 178:1265-1273, 1996). During the study of rfaK, a second open reading frame (lgtF) of 720 bp was found upstream of rfaK. An amino acid sequence homology search of the GenBank and EMBL databases revealed that the amino terminus of LgtF has significant homology with a family of beta-glycosyltransferases involved in the biosynthesis of polysaccharides and O antigen of lipopolysaccharides. The chromosomal copy of lgtF was mutagenized with a nonpolar antibiotic resistance cassette to minimize potential polar effects on rfaK. Tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis and composition analysis of the LOS from the nonpolar lgtF mutant showed that this strain produced a truncated LOS structure which contained a LOS inner core of GlcNAc1Hep2KDO2lipid A but without the addition of lacto-N-neotetraose to HepI or glucose to HepII. These results and the amino acid homology with beta-glycosyltransferases suggest that lgtF encodes the UDP-glucose:LOS-beta-1,4-glucosyltransferase which attaches the first glucose residue to HepI of LOS. Reverse transcriptase PCR and primer extension analysis indicate that both lgtF and rfaK are cotranscribed as a polycistronic message from a promoter upstream of lgtF. This arrangement suggests that completion of the LOS inner core and the initiation of the alpha chain addition are tightly coregulated in N. meningitidis.

Amino Acid Sequence↗
PubMed1996

Inner core biosynthesis of lipooligosaccharide (LOS) in Neisseria meningitidis serogroup B: identification and role in LOS assembly of the alpha1,2 N-acetylglucosamine transferase (RfaK).

A lipooligosaccharide (LOS) mutant of Neisseria meningitidis serogroup B strain NMB (immunotype L3,7,9) was identified in a Tn916 (tetM) mutant bank by loss of reactivity with monoclonal antibody 3F11, which recognizes the terminal Galbeta1-->4GlcNAc epitope in the lacto-N-neotetraose moiety of the wild-type LOS structure. The mutant, designated 559, was found to express a truncated LOS of 3.0 kDa. Southern and PCR analyses demonstrated that there was a single intact Tn916 insertion (class I) in the mutant 559 chromosome. Linkage of the LOS phenotype and the Tn916 insertion was confirmed by transformation of the wild-type parent. Nucleotide sequence analysis of the region surrounding the transposition site revealed a 1,065-bp open reading frame (ORF). A homology search of the GenBank/EMBL database revealed that the amino acid sequence of this ORF had 46.8% similarity and 21.2% identity with the alpha1,2 N-acetylglucosamine transferase (RfaK) from Salmonella typhimurium. Glycosyl composition and linkage analysis of the LOS produced by mutant 559 revealed that the lacto-N-neotetraose group which is attached to heptose I (HepI) and the N-acetylglucosamine and glucose residues that are attached to HepII in the inner core of the parental LOS were absent. These analyses also showed that the HepII residue in both the parent and the mutant LOS molecules was phosphorylated, presumably by a phosphoethanolamine substituent. The insertion of nonpolar and polar antibiotic resistance cartridges into the parental rfaK gene resulted in the expression of LOS with the same mobility as that produced by mutant 559. This result indicated that the inability to add the lacto-N-neotetraose group to the 559 LOS is not due to a polar effect on a gene(s) downstream of rfaK. Our data indicate that we have identified the meningococcal alpha1,2 N-acetylglucosamine transferase responsible for the addition of N-acetylglucosamine to HepII. We propose that the lack of alpha-chain extension from HepI in the LOS of mutant 559 may be due to structural constraints imposed by the incomplete biosynthesis of the LOS inner core.

Amino Acid Sequence↗
PubMed1995

Co-transcription of a homologue of the formamidopyrimidine-DNA glycosylase (fpg) and lysophosphatidic acid acyltransferase (nlaA) in Neisseria meningitidis.

We report the identification of an open reading frame in a serogroup B isolate of Neisseria meningitidis that exhibits high nucleotide and predicted amino acid identity with the fpg gene of Escherichia coli, and its product, formamidopyrimidine-DNA glycosylase (Fapy-DNA glycosylase), a DNA repair enzyme. We further show that the meningococcal fpg is co-transcribed with nlaA, encoding a lysophosphatidic acid acyltransferase, and suggest that the DNA repair enzyme may be involved in the regulation of nlaA or its gene product.

Acyltransferases↗
PubMed1995

Sporadic meningococcal disease in adults: results of a 5-year population-based study.

OBJECTIVE: To define the incidence, demographics, clinical features, and risk factors for sporadic meningococcal disease in adults (> or = 18 years) residing in metropolitan Atlanta. DESIGN: Prospective, population-based surveillance, with retrospective review of clinical and laboratory records. SETTING: Eight-county metropolitan Atlanta area. PATIENTS: All adult patients in whom Neisseria meningitidis was isolated from normally sterile sites (blood, cerebrospinal fluid) during the period 1 December 1988 to 30 November 1993. MEASUREMENTS: Incidence, relative risk, clinical and laboratory parameters, and serogroup of meningococcal isolates. RESULTS: For the 5-year period, 44 (33%) of 132 cases of meningococcal disease in Atlanta occurred in adults (annual incidence, 0.50/100,000 adults per year). Twenty-three (52%) of the 44 adults presented without rash or meningitis, the two most obvious signs of meningococcal disease. Pneumonia, sinusitis, or purulent tracheobronchitis, but without rash, were the likely sources of meningococcal bacteremia in 15 (34%) of the 44 adults. Twelve of the 15 patients with meningococcal respiratory infection were older than 50 years of age or were immunocompromised (or both), and three fourths of the 15 patients had disease caused by serogroups B, Y, and W-135. Overall, two thirds of adults older than 24 years of age with meningococcal disease had one or more immunocompromising conditions (for example, low complement 50 level [CH50], corticosteroid use, congestive heart failure, multiple myeloma, human immunodeficiency virus infection). Meningococcemia or meningococcal meningitis, often caused by serogroup C, were the presentations in 14 of 15 adults 18 to 24 years old; only 2 had an identified underlying condition. CONCLUSIONS: In this 5-year population-based study, one third of all cases of sporadic meningococcal disease occurred in adults. Over half of the adults presented without rash or meningitis. Pneumonia, sinusitis, and tracheobronchitis are important sources of bacteremic meningococcal disease, especially in immunocompromised patients and elderly persons.

Adolescent↗
PubMed1995

Evaluation of the chick embryo for the determination of relative virulence of Neisseria meningitidis.

The chick embryo model was evaluated as a method to compare virulence between selected strains of Neisseria meningitidis. Inoculation of 13-day-chick embryos via the egg yolk distinguished strains having an LD50 of 10(3) colony forming units (CFU) or greater (low virulence) from those having an LD50 of approximately 10(1) or less (high virulence). A strain of serogroup B and a spontaneous nonpiliated strain of group C were found to be of relatively high virulence while a strain of N. lactamica, a serogroup A carrier strain, and certain nongroupable strains were found to be of low virulence. Strains having an LD50 of 10(2) were not differentiated from either of these. Alternatively, inoculation of the chorioallantoic membrane (CAM) of 9-day-old chick embryos statistically differentiated most strains of N. meningitidis although inoculation via this route was less sensitive.

Allantois↗