Severity of Meningococcal Disease Associated with Genomic Bacterial Load

Darton, Thomas C.; Guiver, Malcolm; Naylor, Simone; Jack, Dominic; Kaczmarski, Edward B.; Borrow, Raymond; Read, Robert C.

doi:10.1086/596707

Cited by 102 publications

(78 citation statements)

References 34 publications

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“…We could not correlate DBL with mortality because none of our children died. Our data are in accordance with previous reports showing a relationship between DBL and worse outcome [34,10 ] and prolonged length of hospital stay [9] in patients with severe pneumococcal infections such as pneumonia and meningitis; as well as occurred in patients with meningococcal meningitis in whom there was an association between bacterial load and mortality, complications, sequelae and length of hospital stay [35].…”

Section: P=04)supporting

confidence: 93%

DNA bacterial load in children and adolescents with pneumococcal pneumonia and empyema

Muñoz-Almagro

Gala

Selva

et al. 2010

Eur J Clin Microbiol Infect Dis

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Section: P=04)supporting

confidence: 93%

DNA bacterial load in children and adolescents with pneumococcal pneumonia and empyema

Muñoz-Almagro

Gala

Selva

et al. 2010

Eur J Clin Microbiol Infect Dis

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“…This estimate of the bacterial DNA load in patient specimens may have clinical utility. Several studies have demonstrated that bacterial load measured by PCR correlates with disease severity and that the bacterial load is predictive of which patients are likely to become severely ill (35,37,41,42,52,53). Two studies independently identified a bacterial load of 1 ϫ 10 3 genome copies per ml of blood as a critical threshold above which patients had an increased risk of developing septic shock with E. coli (37), S. aureus (37), or Streptococcus pneumoniae (42), suggesting that quantitative measurement of the bacterial DNA load in blood may have clinical value.…”

Section: Discussionmentioning

confidence: 99%

“…In order to estimate the true concentration of pathogen DNA available in whole blood for molecular analysis from patients with bloodstream infections, we analyzed the data available in the literature. Organism-specific quantitative PCR has been used to measure the bacterial DNA present in whole-blood specimens from patients with sepsis, pneumonia, or suspected bloodstream infections (13,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). Each of these studies analyzed whole-blood specimens from patients with suspected or confirmed infections rather than spiked samples for which the genome-to-viable cell ratio is expected to be close to 1:1.…”

Section: Repeated Analytical Testing By Pcr/esi-msmentioning

confidence: 99%

Improved Sensitivity for Molecular Detection of Bacterial and Candida Infections in Blood

et al. 2014

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The rapid identification of bacteria and fungi directly from the blood of patients with suspected bloodstream infections aids in diagnosis and guides treatment decisions. The development of an automated, rapid, and sensitive molecular technology capable of detecting the diverse agents of such infections at low titers has been challenging, due in part to the high background of genomic DNA in blood. PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) allows for the rapid and accurate identification of microorganisms but with a sensitivity of about 50% compared to that of culture when using 1-ml wholeblood specimens. Here, we describe a new integrated specimen preparation technology that substantially improves the sensitivity of PCR/ESI-MS analysis. An efficient lysis method and automated DNA purification system were designed for processing 5 ml of whole blood. In addition, PCR amplification formulations were optimized to tolerate high levels of human DNA. An analysis of 331 specimens collected from patients with suspected bloodstream infections resulted in 35 PCR/ESI-MS-positive specimens (10.6%) compared to 18 positive by culture (5.4%). PCR/ESI-MS was 83% sensitive and 94% specific compared to culture. Replicate PCR/ESI-MS testing from a second aliquot of the PCR/ESI-MS-positive/culture-negative specimens corroborated the initial findings in most cases, resulting in increased sensitivity (91%) and specificity (99%) when confirmed detections were considered true positives. The integrated solution described here has the potential to provide rapid detection and identification of organisms responsible for bloodstream infections.

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“…Moreover, heparin is not known to alter gene expression in Neisseria. Bacterial loads in patients with fulminant disease can reach up to 10 9 bacteria/ml (9,17,44). In order to prepare the inoculum for use in blood, N. meningitidis was grown overnight on GC agar plates and cultured in GC broth to early exponential phase (optical density [OD], 0.5 to 0.6).…”

Section: Methodsmentioning

confidence: 99%

Analysis of the Regulated Transcriptome of Neisseria meningitidis in Human Blood Using a Tiling Array

et al. 2012

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Neisseria meningitidis is the major cause of septicemia and meningococcal meningitis. During the course of infection, the bacterium must adapt to different host environments as a crucial factor for survival and dissemination; in particular, one of the crucial factors in N. meningitidis pathogenesis is the ability to grow and survive in human blood. We recently showed that N. meningitidis alters the expression of 30% of the open reading frames (ORFs) of the genome during incubation in human whole blood and suggested the presence of fine regulation at the gene expression level in order to control this step of pathogenesis. In this work, we used a customized tiling oligonucleotide microarray to define the changes in the whole transcriptional profile of N. meningitidis in a time course experiment of ex vivo bacteremia by incubating bacteria in human whole blood and then recovering RNA at different time points. The application of a newly developed bioinformatic tool to the tiling array data set allowed the identification of new transcripts-small intergenic RNAs, cis-encoded antisense RNAs, mRNAs with extended 5= and 3= untranslated regions (UTRs), and operons-differentially expressed in human blood. Here, we report a panel of expressed small RNAs, some of which can potentially regulate genes involved in bacterial metabolism, and we show, for the first time in N. meningitidis, extensive antisense transcription activity. This analysis suggests the presence of a circuit of regulatory RNA elements used by N. meningitidis to adapt to proliferate in human blood that is worthy of further investigation.

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Severity of Meningococcal Disease Associated with Genomic Bacterial Load

Cited by 102 publications

References 34 publications

DNA bacterial load in children and adolescents with pneumococcal pneumonia and empyema

DNA bacterial load in children and adolescents with pneumococcal pneumonia and empyema

Improved Sensitivity for Molecular Detection of Bacterial and Candida Infections in Blood

Analysis of the Regulated Transcriptome of Neisseria meningitidis in Human Blood Using a Tiling Array

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