Definition
• Respiratory infection with a new strain of H1N1, a novel swine-origin influenza A RNA virus that resulted from the combination of a previous triple reassortment of bird, swine, and human flu viruses further combined with a Eurasian swine flu virus
Pathogenesis
• In typical uncomplicated infections, viral replication remains limited to the mucosal lining of the pharynx and upper tracheobronchial tree
• Determinants of progression to fatal pulmonary disease are poorly understood but likely include factors such as age, immune and underlying health status, preexisting immunity to viral antigens (principally hemagglutinin), and pharyngeal bacterial flora
• At autopsy, the viral antigen was identified mainly in the tracheobronchial epithelium and submucosal glands and to a lesser extent in bronchiolar epithelium, alveolar epithelial cells, and macrophages
• Individuals older than 60 years were less vulnerable to the infection with 2009 A/H1N1 virus than with seasonal influenza viruses, presumably because of immunological protection induced by prior exposure to previously circulating A/H1N1 viruses
Clinical features
Epidemiology
• In June 2009, the World Health Organization (WHO) described it as the first influenza pandemic in 41 years. The pandemic began to taper off in November 2009, and in August 2010, the WHO announced the end of the H1N1 pandemic
• First identified from patients in Mexico and the United States
• Affected predominantly the young during the pandemic
• Over 500,000 confirmed cases were reported with more than 17,000 deaths worldwide: responsible for approximately 4% of the 250,000 to 500,000 annual influenza deaths during the pandemic
• Virus is spread in the same way that seasonal flu spreads: either directly from droplets from the cough or sneeze of an infected person or by touching contaminated surfaces, then touching the eyes, mouth, or nose
• The contagious period is not well-defined; it most likely starts one day before symptoms appear and lasts about 7 days while the individual has symptoms; it may be a longer period for children
Presentation
• Typical symptoms are similar to seasonal viruses and include fever, coughing, headache, body aches, sore throat, and runny nose
• Gastrointestinal complaints can be present
• In severe cases, patients generally begin to deteriorate around 3 to 5 days after symptom onset; deterioration is rapid, and many patients progress to respiratory failure within 24 hours, requiring immediate admission to an intensive care unit for respiratory support
Prognosis and treatment
• Higher mortality rates were seen in patients with underlying medical conditions such as obesity, cardiorespiratory diseases, and pregnancy
• H1N1 flu is sensitive to the antiviral drugs oseltamivir phosphate (Tamiflu) and zanamivir (Relenza), which can be used for treatment and prevention. They are most effective when taken within 48 hours of the start of flu symptoms. Most people have recovered without treatment; however, treatment is recommended for those with more severe symptoms or those in an at-risk group
Pathology
Gross
• Increased lung weights and solid consistency
• Zones of edema, hemorrhage, or necrosis are noted on the internal surface of the larynx and trachea
Histology
• Tracheitis and bronchitis, with focal or extensive epithelial ulceration, denudation, squamous metaplasia, and submucosal inflammation
• Alveolar septal edema, type II pneumocytic hyperplasia, hyaline membranes, fibrin thrombi in the vascular lumen, and necrosis of the bronchiolar walls
• Subendothelial inflammatory infiltrate with partial loss and adherence of the endothelium seen in medium and small caliber intrapulmonary vessels is characteristic but not pathognomonic for influenza
• About half of the cases show focal intraalveolar exudates
• Erythrophagocytosis and phagocytosis of inflammatory cells in the liver, spleen, and bone marrow (seen also in lethal cases of avian influenza A [H5N1 virus]) was found in some patients
Immunopathology/special stains
• Point of care test screening with rapid influenza diagnostic test (RIDT); performed on nasopharyngeal swabs; detects influenza viral nucleoprotein antigen
• rRT-PCR Swine Flu Panel assay performed on nasopharyngeal swabs is the gold standard
• The sensitivity of RIDTs for detecting novel influenza A (H1N1) virus infections ranges from 10% to 70%. Therefore, a negative RIDT result does not rule out novel influenza A (H1N1) virus infection. Also, this test cannot distinguish influenza infections caused by novel influenza A viruses from those caused by seasonal influenza A viruses
Main differential diagnosis
• Other influenza A and B viruses