Histopathological and immunohistochemical findings of 20 autopsy cases with 2009 H1N1 virus infection

Abstract

, were histopathologically analyzed. Hematoxylin-eosin staining, immunohistochemistry for type A influenza nucleoprotein antigen, and real-time reverse transcription-PCR assay for viral RNA were performed on formalin-fixed and paraffin-embedded specimens. In addition, the D222G amino acid substitution in influenza virus hemagglutinin, which binds to specific cell receptors, was analyzed in formalinfixed and paraffin-embedded trachea and lung sections by direct sequencing of PCR-amplified products. There were several histopathological patterns in the lung according to the most remarkable findings in each case: acute diffuse alveolar damage (DAD) with a hyaline membrane (four cases), organized DAD (one case), acute massive intra-alveolar edema with variable degrees of hemorrhage (three cases), neutrophilic bronchopneumonia (five cases) and tracheobronchitis with limited histopathological changes in alveoli (four cases). In two cases, the main findings were due to preexisting disease. Influenza virus antigen was only detected in the respiratory tract in 10 cases by immunohistochemistry. The antigen was detected in type II pneumocytes (three cases) in the epithelial cells of the trachea, bronchi and glands (six cases), and in the epithelial cells in both of the above (one case). The four cases with acute DAD presented with antigen-positive type II pneumocytes. In one case, the D222G substitution was detected in the lung as a major sequence, although 222D was prominent in the trachea, suggesting that selection of the viral clones occurred in the respiratory tract. In five

Diagnosis and clinic-pathological findings of influenza virus infection in Brazilian pigs

“…The frequent staining of bronchial glands observed here is a common finding in human seasonal and pandemic influenza infection (Gill et al 2010, Nakajima et al 2012. Glandular staining was observed in pandemic H1N1 2009 virus infection in pigs (Sreta et al 2009), however it is not usual in endemic infections (Vincent et al 1997).…”

Respiratory viruses as a cause of sudden death

“…The most pathogenic and epidemic viruses like RSV or influenza viruses are also those commonly identified in sudden death [18]. Pandemic influenza viruses are responsible for a larger number of deaths than the seasonal influenza virus [10]. Second, infectious part is also based on host immunodeficiency that mainly affects children under 2 years at a period of their development where they lose the protection provided by maternal antibodies while still having an immature immune system.…”

“…The epidemiology of sudden deaths associated with respiratory virus responds to obvious seasonal changes and coincides with epidemic winter peaks of these viruses, with the notable exception of the EV group mainly circulating during summer and autumn. Some of these viruses have a specific clinical presentation; EV often associate heart and lung damage; ADV are also responsible for gastroenteritis; finally, the pandemic FluA is responsible for more deaths than seasonal virus due to increased virulence of the pathogen, its circulation within an immunologically naïve population leading to more readily systemic spread through the body [10]. Other viruses involved in common childhood diseases such as herpes simplex, Varicella Zoster virus (VZV), Epstein-Barr virus, cytomegalovirus, human herpes virus type 6, and Parvovirus B19 have also been detected in lungs of deceased infants, but their involvement in the death remained sometimes uncertain [11].…”

Histopathological Findings of Lung with A/H1N1pdm09 Infection-Associated Acute Respiratory Distress Syndrome in the Post-Pandemic Season

“…According to the World Health Organization, a global A/H1N1pdm09 pandemic occurred from June 2009 to August 2010 (2). Several fatal cases of A/H1N1pdm09 infection-associated acute respiratory distress syndrome (ARDS) were reported during the 2009-2010 pandemic season (3)(4)(5), and among them, the first autopsy case in Japan was examined in detail using pathological and molecular biological techniques (6). Pathologically, the case (hereafter referred to as``case 2009'') was complicated by viral pneumonia that developed into ARDS, and the patient subsequently died from a respiratory failure.…”

“…No specific findings were noted in the extrarespiratory organs. The formalin-fixed paraffin-embedded (FFPE) samples from the trachea and bronchi and 50 lung sections were analyzed as previously described (5,6). Briefly, hematoxylin and eosin staining was performed for histological examination; immunohistochemical staining to detect influenza virus type A nucleoprotein antigen (InfA-NP); sequencing to analyze the receptor binding site of the viral hemagglutinin (HA) protein; and a real-time RT-PCR to quantify A/H1N1pdm09 RNA copy number, in the FFPE lung sections.…”