posted on Nov, 26 2009 @ 06:17 PM
Pathological Changes Associated with the 2009 H1N1 Virus
To the Editor: Between April 23, 2009, and May 15, 2009, we performed 15 autopsies on deceased patients in whom probable influenza had been diagnosed
either clinically or macroscopically. Small samples of lung tissue were obtained and taken for analysis to the Institute of Epidemiological Diagnosis
and Reference in Mexico City. Five infections with the 2009 pandemic influenza A (H1N1) virus were confirmed with the use of a real-time
reverse-transcriptase–polymerase-chain-reaction assay, after it was determined that these patients were seronegative for influenza B virus,
respiratory syncytial virus, parainfluenza virus (types 1, 2, and 3), and adenovirus.1 From these five patients, organ samples were collected, fixed
in 10% formalin, embedded in paraffin, and stained with hematoxylin and eosin. In the remaining 10 patients in whom the 2009 H1N1 virus was not
detected, histopathological analyses identified bacterial pneumonia.
All five patients with diagnosed 2009 H1N1 influenza had been residents of Mexico City. Four of them were young adults (ages 22, 26, 28, and 37 years)
who were hospitalized with the presumptive diagnosis of influenza. These patients were initially treated with antibiotics for bacterial pneumonia. The
fifth patient was an 83-year-old woman with a diagnosis of cerebral hemorrhage, who had no clinical signs of influenza but showed characteristics of
hemorrhagic pneumonia on macroscopic evaluation. The patients had died 7 to 13 days after the onset of influenza symptoms.
On autopsy for all five patients, the right and left lungs had increased in weight (650 to 1200 g for each lung; normal, 450 g) and had a solid
consistency (see Fig. 1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). In four patients, zones of edema,
hemorrhage, or necrosis were observed in the upper respiratory tract on the internal surface of the larynx and trachea, as reported in previous cases
of seasonal influenza.2,3 All five patients showed evidence of pulmonary damage and signs of acute interstitial lesions, as noted in patients with
avian influenza A (H5N1) virus infection.3,4
In four patients, we observed hyaline membranes, alveolar septal edema, hyperplasia of type II pneumocytes, fibrin thrombus in the vascular lumen, and
necrosis of the bronchiolar walls; three patients had inflammatory infiltrate below the endothelium and partial loss and adherence of the endothelium
in the medium- and small-caliber intrapulmonary blood vessels (Figure 1). These histologic changes are characteristics of influenza though not
pathognomonic. In three patients, we observed pneumonia foci with intraalveolar exudates without evidence of bacterial colonies; however, nearly all
the patients had received antibiotic treatment. In two patients, we observed erythrophagocytosis and phagocytosis of inflammatory cells in the liver,
spleen, and bone marrow, which is similar to observations in lethal cases of infection with the avian influenza A (H5N1) virus2 (Fig. 2 and 3 in the
Supplementary Appendix). One patient had focal centrilobular necrosis of the liver and hemorrhagic necrosis of the adrenal gland cortex, and acute
tubular necrosis was observed in another patient.
[edit on 26-11-2009 by blc4r4]