Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This overview summarizes studies conducted since 1970 on the laboratory diagnosis of bacterial meningitis at the Naval Medical Research Unit No. 3. These investigations demonstrated that counterimmunoelectrophoresis (CIE), agglutination of sensitized staphylococcal cells or latex particles, and enzyme-linked immunosorbent assay (ELISA) effectively detect and identify specific antigens in the cerebrospinal fluid of patients with meningococcal, pneumococcal, and Haemophilus meningitis. ELISA was the most sensitive of these methods and CIE the least sensitive. ELISA was also used to measure antibodies to meningococcal outer membrane protein antigens in patients. Finally, high rates of group A meningococcal nasopharyngeal carriage were found in group A meningococcal meningitis patients and populations associated with group A patients, but not in populations that were not associated with group A disease.
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PMID:Laboratory diagnosis of bacterial meningitis. 180 98

Haemophilus influenzae type b is a major cause of bacterial meningitis and other invasive diseases in children under four years of age. One surface antigen, the type b capsular polysaccharide, polyribosylribitol phosphate (PRP), is a primary virulence factor of the organism. Antibody directed against PRP is protective; however, the purified polysaccharide is poorly immunogenic in young children. Polysaccharide-protein conjugate vaccines have been prepared which are significantly more immunogenic and efficacious in young children compared to the plain polysaccharide vaccine. Noncapsular surface antigens may also play a role in the virulence of H. influenzae. Some mutants (or phase variants) which differ in lipooligosaccharide (LOS) structure exhibit decreased virulence in the infant rat model of bacteremia. Proteins including the IgA protease, pili, a 98K outer membrane protein (OMP) as well as OMPs P1, P2 and P6 have also been examined in considerable detail, but whether they have a role in the virulence of the organism remains to be determined. However, antibody directed against the 98K OMP as well as P1, P2 and P6 is protective in the infant rat model of bacteremia. The role of antibody directed against LOS epitopes in protection is less clear, due at least in part, to phase variation in LOS antigens. Characterization of one surface antigen of H. influenzae type b, the capsular polysaccharide, already has led to the prevention of many cases of Haemophilus disease. Characterization of the noncapsular antigens together with a more detailed understanding of the mechanisms of virulence, most likely will permit development of even better vaccines, and possibly better treatment modalities, in the future.
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PMID:Haemophilus influenzae: surface antigens and aspects of virulence. 219 7

Haemophilus influenzae is a gram-negative rod, causing severe infections in childhood, including meningitis, sepsis, epiglottits, pneumonia and otitis. Most of the invasive infections are due to serotype b. Since ampicillin-resistance is increasing, modern cephalosporines like cefotaxime and ceftriaxone are the antibiotics of choice in severe disease. Bacterial meningitis due to Haemophilus influenzae and epiglottitis are both still life-threatening diseases with a lethality of 5% to 25%, and there are severe sequelae in 35% of meningitis cases. Efforts have been made to develop efficacious vaccines. While immunogenicity of type b polysaccharide was low in the high-risk age (below 18 months), conjugated vaccines with either diphtheria-toxoid or Neisseria meningitis outer membrane protein and the Hib polysaccharide were found to be strongly immunogenic even in the first months of life. These vaccines show every few side-effects and can easily be combined with other immunizations such as DPT and DT. Thus, the incidence of invasive infections due to Haemophilus influenzae type b might decline in future.
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PMID:[Haemophilus influenzae type B. Disease and prevention]. 219 58

Haemophilus influenzae type b remains the major cause of bacterial meningitis in infants and children. Serum antibodies against the capsular polysaccharide--polyribosylribitolphosphate (PRP)--are protective, but its immunogenicity is poor in children under two years of age. Clinical trials actually in progress concerning an association of PRP with Bordetella pertussis are presented. Other vaccinal preparations are possible, such outer membrane protein, but prospects offered by polysaccharide-protein conjugates appear as the most encouraging.
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PMID:[Prospects for the vaccinal prevention of Haemophilus influenzae type b meningitis]. 634 45

Haemophilus influenzae type b (HIb) is the most common cause of bacterial meningitis in children with a mortality rate ranging from 1.6% to 14%. Most patients have a 2-3 day history of symptoms prior to admission. A few have fulminating disease with rapid neurological deterioration. Review of 191 cases of HIb meningitis revealed a mortality rate of 2.1% but all who died had fulminating meningitis (FM). Four of six patients with FM died. FM patients had symptoms for less than 24 hours before rapid neurological deterioration with increased ICP, seizures, coma and/or respiratory arrest. Review of 10 FM cases revealed that on admission, 5 had hypotension, 3 had thrombocytopenia, and 8 had coma. Typical CSF changes were seen in only 7. All fatal cases died within 24 hours. Brain swelling and tonsillar herniation were found at autopsy. SDS-PAGE outer membrane protein subtyping did not show one "killer strain". Animal and autopsy data suggest that diminished CSF outflow and cerebral edema contribute to increased ICP. To improve survival of FM patients, initial treatment must (1) decrease ICP below levels impairing cerebral perfusion, (2) maintain adequate ventilation and blood pressure, and include (3) LP when stable, (4) antibiotics, and (5) close monitoring. Utilizing these principles, two FM patients survived without major sequelae.
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PMID:Fulminating haemophilus influenzae b meningitis. 670 99

Strains of Haemophilus influenzae type b were collected as part of an epidemiological study of bacterial meningitis in the North East Thames Region (NETR) of England. Subclones of H. influenzae were identified by outer-membrane protein typing and multilocus enzyme electrophoresis. These were compared with subclones of H. influenzae type b isolated from elsewhere in the UK. The subclone ET 12.5/OMP 3L was identified in 68% of isolates from cases of meningitis from the NETR. In the isolates from elsewhere in the UK, this subclone was identified in 79% of sterile-site isolates and 91% of isolates from non-sterile sites. This subclone predominated in patients of different ages and from different ethnic groups, which suggests that non-Caucasians are infected with the subclone predominating locally. Since ET 12.5/OMP 3L subclone is the most abundant strain isolated in virtually all other Western European countries, these results provide additional evidence that the genetic diversity in the H. influenzae type b population in Europe is relatively restricted.
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PMID:Clonal analysis of Haemophilus influenzae type b isolates in the United Kingdom. 760 55

Haemophilus influenzae type b is a major cause of bacterial meningitis in young children. Antibodies against the outer membrane protein P2 are protective in the infant rat model of bacteremia. To identify conserved, surface-exposed, and protective epitopes of P2, 17 overlapping peptides covering the entire sequence of the protein were synthesized. Antisera from mice, guinea pigs, and rabbits raised against chromatographically purified P2 were tested for their reactivities to the peptides by enzyme-linked immunosorbent assays (ELISA). Three major linear immunodominant B-cell epitopes were mapped to residues 53 to 81, 241 to 265, and 314 to 341 of mature P2. Human convalescent-phase antisera also reacted strongly with these three epitopes. Rabbit antisera against all peptide-keyhole limpet hemocyanin conjugates except two peptides containing residues 8 to 19 and 302 to 319 recognized the corresponding peptides in ELISA and reacted with P2 on immunoblots. Immunization with all unconjugated peptides, except the 19 N-terminal residues, induced very strong peptide-specific antibody responses, and these antisera reacted with P2 on immunoblots. Rabbit antisera raised against peptides corresponding to residues 1 to 14, 125 to 150, 193 to 219, and 241 to 319 also recognized P2 purified from H. influenzae nontypeable isolates. Identification of these immunodominant B-cell epitopes and conserved regions is a first step toward the rational design of a universal H. influenzae vaccine.
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PMID:Immunogenicity of overlapping synthetic peptides covering the entire sequence of Haemophilus influenzae type b outer membrane protein P2. 850 Sep 4

Cerebral vascular injury is common in bacterial meningitis, but the role of microbial factors associated with this phenomenon is unclear. Escherichia coli S-fimbriae and outer membrane protein A (OmpA) have been shown to promote binding and invasion of E. coli to brain microvascular endothelial cells, respectively. Using the cranial window model, we compared the response of pial arterioles in experimental animals exposed to E. coli with and without S-fimbriae or OmpA after intracarotid injection to animals receiving saline (control). After 3 h, pial arteriolar diameter had progressively increased to 144 +/- 23 (SD)% of the baseline value in animals exposed to S-fimbriated E. coli and to 131 +/- 12% of the baseline value in animals exposed to nonfimbriated E. coli. Analysis of variance with Bonferroni post hoc comparisons revealed that at 2 h the pial arteriolar response to S-fimbriated E. coli was significantly different from control (p = 0.0142). After 3 h, the S-fimbriated E. coli group was significantly different from both the control and the nonfimbriated group (p = 0.0024 and 0.0163, respectively). The nonfimbriated group showed a trend of progressive vasodilation, which was not significantly different from the control. After 3 h, pial arteriolar diameter progressively increased to 156 +/- 14% of baseline in animals exposed to OmpA+ E. coli and 151 +/- 24% of baseline to OmpA- E. coli. The vasodilatory response to OmpA+ and OmpA- E. coli was statistically different from control (p = 0.0004 and 0.0010, respectively) but not different from each other. These data suggest that, although cerebral vasodilatory response to E. coli is multifactorial, binding plays an important role in initiating the vasodilation and bacterial invasion does not enhance the vasodilatory response in the cerebral microvasculature.
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PMID:The effects of Escherichia coli S-fimbriae and outer membrane protein A on rat pial arterioles. 884 32

The purpose of the present study was to generate monoclonal antibodies (mAbs) against conserved epitopes of B meningococcus which could be applicable to the immunoscreening of bacterial meningitis. Three mAbs reactive to a 46-kDa protein conserved in eight sero-groups and several sero(sub)types of Neisseria meningitidis were selected for the present study. No reaction was detected with whole-cell lysates of Staphylococcus aureus. Streptococcus pneumoniae, Haemophilus influenzae type b or Escherichia coli. Two of these mAbs recognized 46-kDa epitopes in four other Neisseria spp, and the third, MC3.13, cross-reacted only with N. lactamica. All mAbs reacted with whole-cell lysates from a N. meningitidis mutant strain lacking the class 1 outer membrane protein (43-47 kDa). Immunoelectron microscopy revealed a cytoplasmic location for the 46-kDa protein. The MC3.13 monoclonal antibody is potentially applicable to a rapid screening of bacterial meningitis.
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PMID:Monoclonal antibodies against conserved epitopes of a 46-kDa protein from Neisseria meningitidis. 919 50

Class 1 outer membrane protein PorA of Neisseria meningitidis is a vaccine candidate against bacterial meningitis. Antibodies against PorA are able to induce complement-mediated bacterial killing and thereby play an important role in protection against meningococcal disease. Bactericidal antibodies are all directed against variable regions VR1 and VR2 of the PorA sequence, corresponding to loops 1 and 4 of a two-dimensional topology model of the porin with eight extracellular loops. We have determined the crystal structure to 2.6 A resolution of the Fab fragment of bactericidal antibody MN12H2 against meningococcal PorA in complex with a linear fluorescein-conjugated peptide TKDTNNNL derived from the VR2 sequence of sero-subtype P1.7,16 (residues 180-187) from meningococcal strain H44/76. The peptide folds deeply into the binding cavity of the Fab molecule in a type I beta-turn, with the minimal P1.16 epitope DTNNN virtually completely buried. The structure reveals H-bonds and van der Waals interactions with all minimal epitope residues and one essential salt bridge between Asp-182 of the peptide and His-31 of the MN12H2 light chain. The key components of the recognition of PorA epitope P1.16 by bactericidal antibody MN12H2 correspond well with available thermodynamic data from binding studies. Furthermore, they indicate the structural basis of an increased endemic incidence of infection by group B meningococci in England and Wales since 1981 associated with the occurrence of an Neisseria meningitidis escape mutant (strain-MC58). The observed three-dimensional conformation of the peptide provides a rationale for the development of a synthetic peptide vaccine against meningococcal disease.
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PMID:Bactericidal antibody recognition of a PorA epitope of Neisseria meningitidis: crystal structure of a Fab fragment in complex with a fluorescein-conjugated peptide. 929 71


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