New therapies and vaccines for meningococcal disease.
Meningococcal disease (MCD) is an important cause of morbidity and mortality. The pathophysiology consists of a complex interaction of bacterial and host factors, triggered by the release of endotoxin which initiates the inflammatory cascade, resulting in multi-organ failure, coagulopathy, capillary leak, metabolic derangement and eventually death. Prompt recognition and aggressive management are essential in reducing mortality. Over the past decade, there has been intense research into novel therapies and vaccines, with largely disappointing results. Therapies have been broadly divided into anti-endotoxin and anti-TNF-alpha therapies, treatment aimed at correcting coagulopathy and at blood purification and anti-inflammatory cytokine therapy. The reasons for the disappointing results in the search for new therapeutic strategies are difficult to identify. The disordered physiology in MCD results from a complex interaction of several mediators; therefore attempts to correct this by altering just one step represents a gross oversimplification of the process. In addition, the experimental model of endotoxaemia, which is often used, is a poor representation of an acutely ill patient with rapidly progressive shock. There have been several small or poorly designed trials, which have failed to reach definite conclusions. In order to yield conclusive results any future trials must be multicentre, randomised, controlled trials, but these are expensive and, in practice, difficult to conduct. The BPI trial (vide infra) was a significant step forward in this regard and demonstrated the ability to organise a large multicentred trial which can act as a template for future trials. Although the results were not significant there was an overall trend towards improved outcome in the treatment arm. Whilst the development of effective therapies and vaccines are awaited, the priorities at present must be the prompt recognition and aggressive management of disease.
Carrol
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ED
Institute of Child Health, Royal Liverpool Children's Hospital, NHS Trust (Alder Hey), Eaton Road, Liverpool, L12 2AP, Liverpool, UK. edcarrol@liv.ac.uk
Thomson
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AP
Hart
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CA
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D018946:Chemokine CCL5 / Q000627:therapeutic use; D004731:Endotoxins / Q000037:antagonists & inhibitors; D006801:Humans; D008589:Meningococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013256:Steroids / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D001428:Bacterial Vaccines; D018946:Chemokine CCL5; D004731:Endotoxins; D017472:Receptors, Interleukin-1; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide