Re-emergence of fatal human influenza A subtype H5N1 disease

Abstract

Human disease associated with influenza A subtype H5N1 re-emerged in January, 2003, for the first time since an outbreak in Hong Kong in 1997. Patients with H5N1 disease had unusually high serum concentrations of chemokines (eg, interferon induced protein-10 [IP-10] and monokine induced by interferon gamma [MIG]). Taken together with a previous report that H5N1 influenza viruses induce large amounts of proinflammatory cytokines from macrophage cultures in vitro, our findings suggest that cytokine dysfunction contributes to the pathogenesis of H5N1 disease. Development of vaccines against influenza A (H5N1) virus should be made a priority.

Figure 1

Histological stains of lung tissue from 33-year-old man with H5N1 pneumonia Left panel: intra-alveolar oedema, haemorrhage, and increased fibrin and alveolar macrophages are evident. Haematoxylin and eosin stain used. Right panel: macrophages were shown by use of immunohistochemical staining with antibody to CD68.

Figure 2

Immunohistochemical staining for TNF in lung tissue from patient with H5N1 pneumonia and a patient who died from non-infective illness Stains made with monoclonal antibody SC-7317 (Santa Cruz Biotechnology, Santa Cruz, CA, USA) at a dilution of 1/10 with antigen retrieval. The 33-year-old man with H5N1 pneumonia (left panel) shows greater staining of alveolar epithelial cells than does the control (right panel)