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The number of bacteria in the blood determines the severity of meningococcal disease, predictably perhaps, but only recently shown in a study involving Alder Hey Children's Hospital, Liverpool, and the PHLS Meningococcal Reference Unit (MRU) in Manchester, UK.
Meningococcal disease can present as meningitis or septicaemia, or both; septicaemia carries a mortality of 6–75%. Its severity seems to hinge on patients' serum concentrations of certain cytokines, bacterial lipo-oligosaccharide (LOS) endotoxin, and bacterial capsular polysaccharide antigen. LOS and antigen concentrations may or may not be proportional to bacterial numbers.
The researchers used Taqman polymerase chain reaction (PCR) of a universal meningococcal capsular gene to measure bacterial numbers accurately in blood samples taken at admission and sequentially from children with probable/ possible meningococcal disease. With one gene per cell, the number of genome copies measured per ml of blood equals bacterial load (viable and dead bacteria). Higher bacterial load at admission occurred with severe disease (≥8 on Glasgow Meningococcal Septicaemia Prognostic Score) (median load 8.4 × 106 severe versus 1.1 × 106 mild disease), particularly in septicaemia patients (1.6 × 107 versus 9.2 × 105; p<0.001). Loads were highest in two patients who died (p=0.017).
The method detected higher bacterial loads than other quantitative methods. Whether increased load and greater severity equates with serum bacterial antigen concentration or LOS endotoxin requires more work. The Taqman method, and speedier new PCR technology, the authors envisage, could in future be used to identify patients with the worst disease, who might then benefit from further treatment against cytokines and endotoxin.