Abbreviations PAP: Pulmonary alveolar proteinosis; GMCSF: granulocyte-macrophagecolony stimulating factor; GM-CSFR: GM-CSF receptor; WLL: whole lung lavage; washing of a single right or left lung. Severe influenza cases in paediatric intensive care units in Germany during the pre-pandemic seasons 2005 to 2008 BACKGROUND: Data on complications in children with seasonal influenza virus infection are limited. We initiated a nation-wide three-year surveillance of children who were admitted to a paediatric intensive care unit (PICU) with severe seasonal influenza. METHODS: From October 2005 to July 2008, active surveillance was performed using an established reporting system for rare diseases (ESPED) including all paediatric hospitals in Germany. Cases to be reported were hospitalized children < 17 years of age with laboratory-confirmed influenza treated in a PICU or dying in hospital. RESULTS: Twenty severe influenza-associated cases were reported from 14 PICUs during three pre-pandemic influenza seasons (2005-2008). The median age of the patients (12 males/8 females) was 7.5 years (range 0.1-15 years). None had received vaccination against influenza. In 14 (70%) patients, the infection had been caused by influenza A and in five (25%) by influenza B; in one child (5%) the influenza type was not reported. Patients spent a median of 19 (IQR 12-38) days in the hospital and a median of 11 days (IQR 6-18 days) in the PICU; 10 (50%) needed mechanical ventilation. Most frequent diagnoses were influenza-associated pneumonia (60%), bronchitis/bronchiolitis (30%), encephalitis/encephalopathy (25%), secondary bacterial pneumonia (25%), and ARDS (25%). Eleven (55%) children had chronic underlying medical conditions, including 8 (40%) with chronic pulmonary diseases. Two influenza A- associated deaths were reported: i) an 8-year old boy with pneumococcal encephalopathy following influenza infection died from cerebral edema, ii) a 14-year-old boy with asthma bronchiale, cardiac malformation and Addison's disease died from cardiac and respiratory failure. For nine (45%) patients, possibly permanent sequelae were reported (3 neurological, 3 pulmonary, 3 other sequelae). CONCLUSIONS: Influenza-associated pneumonia and secondary bacterial infections are relevant complications of seasonal influenza in Germany. The incidence of severe influenza cases in PICUs was relatively low. This may be either due to the weak to moderate seasonal influenza activity during the years 2005 to 2008 or due to under-diagnosis of influenza by physicians. Fifty% of the observed severe cases might have been prevented by following the recommendations for vaccination of risk groups in Germany. Influenza belongs to the most frequent vaccine-preventable diseases. Clinical manifestations of influenza infections range from illness with asymptomatic, atypical (i.e., gastro-intestinal) or oligosymptomatic disease to severe toxic progression resulting in death [1, 2] . Elderly people and infants account for the highest morbidity [1, 3, 4] .