4 years later, in an outbreak of a highly pathogenic subtype H7N7 strain in the Netherlands, conjunctivitis was the prominent feature among 89 persons infected; only 7 individuals had an influenza-like illness that was generally mild. However, one fatal case of pneumonia occurred in a man (Fouchier 2004): two days after visiting a poultry farm affected by avian influenza, the 57-year-old veterinarian developed malaise, headache and fever. Eight days later he developed pneumonia, and his condition then deteriorated. He died four days later of acute pneumonia. The only avian influenza strain to cause repeatedly severe disease in humans is the  H5N1 Yuen 1998). So far, the number of human cases has fortunately been relatively low (152 as of 23 January 2006), but the case-fatality rate is high (83/152) (WHO 20051223). The clinical manifestations of influenza H5N1 infection in humans is not well-defined as current knowledge is based on the description of a few hospitalised patients. The spectrum ranges from asymptomatic infection (Katz 1999, Buxton Bridges 2000, Thorson 2006) to fatal pneumonitis and multiple organ failure .Presentation: Initial symptoms of H5N1 influenza may include fever (typically > 38°C), headache, malaise, myalgia, sore throat, cough, and rhinitis (although upper respiratory symptoms may be absent), gastrointestinal manifestations and conjunctivitis (Yuen 1998, Chan 2002). All these symptoms are non-specific and may also be associated with the currently circulating human influenza virus subtypes, H1N1 and H3N2. In two reports, diarrhoea (Hien 2004) was a prominent feature along with shortness of breath (Hien 2004, Chotpitayasunondh 2005). Watery diarrhoea may be present well before pulmonary symptoms develop (Apisarnthanarak 2004). Another report describes a four-year-old boy with severe diarrhoea, followed by seizures, coma, and death, suggesting the clinical diagnosis of encephalitis . avian influenza H5N1 was later detected in cerebrospinal fluid, faecal, throat, and serum specimens (de Jong 2005). Laboratory findings of patients with severe avian influenza H5N1 include:  leucopenia, lymphopenia, impaired liver function with elevated liver enzymes, prolonged clotting times, and renal impairment. The lymphocyte count appears to be the most valuable parameter for identification of patients who are at risk of progression to severe illness (Chan 2002).Clinical Course As of December 2005, about half of the patients diagnosed with clinical avian H5N1 influenza infection have died. Most of these patients had severe disease on admission to hospital. In patients with respiratory failure and fatal outcome, dyspnoea developed after a median of 5 days (range 1.16) in one series (Chotpitayasunondh 2005). Abnormal chest radiographs include interstitial infiltration, patchy lobar infiltrates in a variety of patterns (single lobe, multiple lobes, unilateral or bilateral distributions). Finally, the radiographic pattern progresses to a diffuse bilateral ground-glass appearance, with clinical features compatible with ARDS (Chotpitayasunondh 2005). In the report from Vietnam, major x-ray abnor166 Clinical Presentation: malities include extensive bilateral infiltration, lobar collapse, focal consolidation, and air bronchograms. All patients had dramatic worsening of findings on chest radiography during hospitalisation. The median time from onset of fever to ARDS was 6 days (range 4.13) in one series (Chotpitayasunondh 2005). Pneumothorax may develop in patients during mechanical ventilation (Hien 2004). Pleural effusions are uncommon. There is conflicting information as to the risk factors associated with severe disease and fatal outcome. In the 1997 outbreak in Hong Kong, the factors associated with severe disease included older age, delay in hospitalisation, lower respiratory tract involvement, and a low total peripheral white blood cell count or lymphopenia on admission (Yuen 1998). In this report, patients aged below 6 years usually had a self-limiting acute respiratory disease with fever, rhinorrhoea, and sore throat. In contrast, recent avian H5N1 infections have caused high rates of death among infants and young children (Chotpitayasunondh 2005). The numbers reported are too small to understand whether local factors . i.e., time between onset of symptoms and admission to hospital . or viral virulence factors are responsible for these differences. As H5N1 strains have evolved over the past 10 years (Webster 2006), clinical features of avian influenza infection in humans may well have different characteristics over time. The progression of severe H5N1 infection seems to be different from that of severe diseases observed during earlier influenza pandemics. None of the patients with severe disease reported from Hong Kong (Yuen 1998) and Vietnam (Hien 2004) had evidence of secondary bacterial pneumonia, suggesting that the fatal outcome was due to an overwhelming primary viral pneumonia. This feature is reminiscent of the 1918 pandemic and may pathogenetically be due to a "cytokine storm" (Barry 2004). serotype, first diagnosed in humans in Hong Kong in 1997 (CDC 1997,