Histopathologic and Immunohistochemical Features of Fatal Influenza Virus Infection in Children during the 2003–2004 Season

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Abstract
Background. The Centers for Disease Control and Prevention enhanced national surveillance for influenza-associated deaths among children because of early reports of pediatric deaths during the 2003–2004 influenza season. Methods. We studied lung and upper airway specimens from 47 case patients who died who had at least 1 positive result for influenza virus tests using hematoxylin and eosin, special stains for bacteria and fungi, and immunohistochemical (IHC) assays for influenza A and B viruses and other potential viral and bacterial respiratory pathogens. Results. Nineteen (40%) of the 47 patients were ⩽2 years old, and 26 (55%) were female. Influenza IHC testing identified type A antigens in 26 patients and type B antigens in 1 patient. Influenza antigens were observed focally in bronchoepithelial cells and mucous glands of trachea, bronchi, and larger bronchioli, showing submucosal mononuclear inflammatory infiltrates. IHC assays were the only confirmatory diagnostic test for 5 patients (11%). Significant life-threatening pathological conditions that could be considered the cause of death were present in 36 patients (77%) and included diffuse alveolar damage (12 cases), extensive secondary pneumonia (11 cases), extensive intraalveolar hemorrhage (10 cases), viral pneumonitis (10 cases), myocarditis (6 cases), and meningoencephalitis (1 case). For 9 patients with bronchopneumonia, a bacterial or fungal etiology was determined with IHC assay (3 Staphylococcus infections, 3 group A streptococci infections, 1 Streptococcus pneumoniae infection, 1 Bordetella pertussis infection, and 1 Aspergillus infection). Conclusions. IHC assays are useful for the diagnosis of influenza and bacterial pneumonia. This study underscores the importance of performing autopsies to identify the causes of death in patients with influenza infection.