title: Severity of meningococcal disease associated with genomic bacterial load.
abstract: BACKGROUND
  Diagnostic polymerase chain reaction (PCR) detection of Neisseria meningitidis has enabled accurate quantification of the bacterial load in patients with meningococcal disease.
  
  
  METHODS
  Quantification of the N. meningitidis DNA level by real time-PCR was conducted on whole-blood samples obtained from patients presenting with meningococcal disease to hospitals throughout England and Wales over a 3-year period. Levels were correlated with clinical outcome, infecting serogroup, and host factors including, interleukin-1 genotype (IL-1).
  
  
  RESULTS
  Bacterial loads were available for 1045 patients and were not associated with the age of the patient, delay in sample submission, or administration of antibiotics prior to admission. The median log bacterial load was higher in 95 patients who died (5.29 log(10)copies/mL; interquartile range, 4.41-6.30 log(10)copies/mL) than in 950 patients who survived (3.79 log(10)copies/mL; interquartile range, 2.87-4.71 log(10)copies/mL). Logistic regression revealed that age (odds ratio, 1.04 per 1-year increase in age) and bacterial load (odds ratio, 2.04 per log(10)-copies/mL increase) had a statistically significant effect on the risk of death. Infection with N. meningitidis serogroup C was associated with increased risk of death and an increased bacterial load. Also associated with a higher bacterial load were prolonged hospitalization (duration, >10 days); digit, limb, or soft-tissue loss; and requirement of hemodialysis. Carriage of IL-1RN(+2018) was associated with increased mortality (odds ratio, 2.14; P=.07) but not with a higher bacterial load.
  
  
  CONCLUSIONS
  In meningococcal disease, bacterial load is associated with likelihood of death, development of permanent disease sequelae, and prolonged hospitalization. The bacterial load was relatively higher in patients infected with N. meningitidis serogroup C than in those infected with other serogroups. The effects of age and IL-1 genotype on mortality are independent of a high genomic bacterial load.
authors.affiliation: Department of Infection and Immunity, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Tom
authors.initials: T
authors.lastname: Darton
authors.forename: Malcolm
authors.initials: M
authors.lastname: Guiver
authors.forename: Simone
authors.initials: S
authors.lastname: Naylor
authors.forename: Dominic L
authors.initials: DL
authors.lastname: Jack
authors.forename: Edward B
authors.initials: EB
authors.lastname: Kaczmarski
authors.forename: Raymond
authors.initials: R
authors.lastname: Borrow
authors.forename: Robert C
authors.initials: RC
authors.lastname: Read
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001769:Blood / Q000382:microbiology*; D001774:Blood Chemical Analysis; D002648:Child; D002675:Child, Preschool; D015169:Colony Count, Microbial; D004269:DNA, Bacterial / Q000032:analysis* / Q000235:genetics; D004739:England; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007375:Interleukin-1 / Q000235:genetics; D016015:Logistic Models; D008589:Meningococcal Infections / Q000382:microbiology* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009345:Neisseria meningitidis / Q000235:genetics / Q000302:isolation & purification*; D012720:Severity of Illness Index; D013223:Statistics as Topic; D014852:Wales; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial; D007375:Interleukin-1