Meningococcal bacterial DNA load at presentation correlates with disease severity. (Original Article)

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From: Archives of Disease in Childhood(Vol. 86, Issue 1)
Publisher: BMJ Publishing Group Ltd.
Document Type: Article
Length: 2,723 words

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Aims: To determine bacterial loads in meningococcal disease (MCD), their relation with disease severity, and the factors which determine bacterial load.

Methods: Meningococcal DNA quantification was performed by the Taqman PCR method on admission and sequential blood samples from patients with MCD. Disease severity was assessed using the Glasgow Septicaemia Prognostic Score (GMSPS, range 0-15, severe disease [greater than or equal to] 8).

Results: Median admission bacterial load was 1.6 x [10.sup.6] DNA copies/ml of blood (range 2.2 x [10.sup.4] to 1.6 x [10.sup.8]). Bacterial load was significantly higher in patients with severe (8.4 x [10.sup.6]) compared to milder disease (1.1 x [10.sup.6], p = 0.018). This difference was greater in septicaemic patients (median 1.6 x [10.sup.7] versus 9.2 x [10.sup.5], p < 0.001). Bacterial loads were significantly higher in patients that died (p = 0.017). Admission bacterial load was independent of the duration of clinical symptoms prior to admission, with no difference between the duration of symptoms in mild or severe cases (median, 10.5 and 11 hours respectively). Bacterial loads were independent of DNA elimination rates following treatment.

Conclusion: Patients with MCD have higher bacterial loads than previously determined with quantitative culture methods. Admission bacterial load is significantly higher in patients with severe disease (GMSPS [greater than or equal to] 8) and maximum load is highest in those who die. Bacterial load is independent of the duration of clinical symptoms or the decline in DNA load.

In the industrialised world meningococcal disease (MCD) remains the leading infective cause of death in children outside the neonatal period. (1) The spectrum of clinical presentation is highly variable, featuring meningitis or septicaemia alone or a combination of the two. Patients with meningococcal septicaemia form a heterogeneous group, of whom 30% require intensive care therapy, and have reported mortality rates ranging from 6 to 75%. (2 3) It is not fully understood why there is such a wide range in the clinical spectrum of MCD. Severity of MCD is positively correlated with the patients' serum cytokine concentrations, for example tumour necrosis factor [alpha] (TNF-[alpha]), interleukin 1[beta] (IL-1[beta]), IL-6 IL-12, and leukaemia inhibitory factor, (4) and also with serum endotoxin (lipo-oligosaccharide, LOS) (4) and serum meningococcal polysaccharide antigen concentrations. (5) LOS initiates the cytokine cascade seen in severe MCD and thus potentiates disease progression. It is not clear whether LO S and antigen concentrations are proportional to bacterial load. This study examines the relation between bacterial load and disease severity in MCD.

Bacterial loads in the order of [10.sup.4] and [10.sup.5] colony forming units (CFU) per ml of cerebrospinal fluid or blood, respectively, have been shown in patients with MCD using a quantitative direct plating procedure (QDP). (6) Patients with Haemophilus influenzae and Streptococcus pneumoniae infections with greater than 100 CFU/ml of blood (generally greater than [10.sup.3] CFU/ml) were significantly more likely to have invasive disease (meningitis and epiglottis), compared to patients with fewer than 100 CFU/ml of blood (92% versus 9.5% respectively). (7) This study did not show such a clear cut association...

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Gale Document Number: GALE|A83028180