Arenaviral Haemorrhagic Fevers

Three arenaviruses--Lassa, Junin and Machupo--cause severe haemorrhagic disease in humans: Lassa fever, Argentine haemorrhagic fever and Bolivian haemorrhagic fever, respectively. These conditions are a source of considerable economic hardship in endemic areas and remain a worldwide concern for public-health officials. They are characterised by an insidious onset of influenza-like symptoms followed, in severe cases, by a generalised bleeding diathesis, encephalopathy and death. Central to studies of their pathogenesis is evidence for cellular dysfunction disproportionate to overt histopathology. Recent studies of patients with Lassa fever indicate that platelet and possibly endothelial-cell dysfunction play an important role in the bleeding tendency. The platelet defect appears to be mediated by an inhibitory factor in plasma; the nature of this is uncertain but it seems to be neither viral protein nor virus antibody. A similar inhibitor has since been demonstrated in patients with Argentine haemorrhagic fever. Plasma from patients with Lassa fever also profoundly modulates the amount of superoxide generated by normal neutrophils in response to the chemotactic peptide f-met-leu-phe, suggesting the inhibitor(s) has global effects on cellular function. These findings may have important implications for future therapeutic strategies.