Influenza Pandemics of 1918 and 2009

A Comparative Account

Madhu Khanna; Latika Saxena; Ankit Gupta; Binod Kumar; Roopali Rajput


Future Virology. 2013;8(4):335-342. 

In This Article

Clinical Manifestations

Influenza infection is self-limiting in humans, but the virus is notorious for causing substantial mortality and morbidity worldwide. Clinical features of influenza virus infection in humans encompass a wide spectrum, from mild rhinitis and coryza, to severe, fulminant infections such as pneumonia and acute respiratory distress syndrome. Although a variety of specimens can be collected for the diagnosis of influenza virus infection, the yield varies. Nasal secretions are considered to be the best specimen for the diagnosis of influenza virus followed by throat swab, urine and serum.[22]

Pandemic and seasonal influenza virus infections share similar signs and symptoms, which make it difficult to differentiate between the diseases caused by the two. The 1918 influenza virus infection was associated with acute onset of chills, frequent epistaxis, myalgia and prostration. The infection had a deleterious and suppressive effect on the bone marrow leading to splenomegaly and rendering the host vulnerable to secondary bacterial infections.[5] Extensive organ involvement was an outstanding feature of the 1918 H1N1 pandemic.

In comparison to the 1918 virus infection, the clinical features of the 2009 pandemic were milder. The most common signs and symptoms among A(H1N1)pdm09-positive in-patients were cough, malaise, headache and fever. At the time of presentation, dyspnea, cyanosis and prostration were significantly associated with the risk of death amongst the virus-positive in-patients.[23] Studies from New York City based on investigation of deaths associated with A(H1N1)pdm09 infection suggest that tracheitis and/or bronchitis was present in all cases, with diffuse alveolar damage associated with viral pneumonia as the primary pathology. Second, influenza viral antigen was distributed predominantly in the tracheobronchial epithelium and submucosal glands, and, to a lesser extent, in bronchiolar epithelium and alveolar epithelial cells and macrophages. Finally, bacterial pneumonia was observed in 55% of the cases and comorbidities in 91% of adult and adolescent decedents (with obesity in 72%). These findings were strikingly similar to the published studies on autopsies based on the 1918 and 1957 pandemics.[24]

Early in the pandemic, the disease overwhelmingly occurred in children and younger adults, with cough and fever as the most prevalent clinical symptoms of the confirmed cases. The unique features of the A(H1N1)pdm09 infection were the complaints of diarrhea and vomiting in a significant number of patients.[25] In severe cases, pneumonia and mild fibrosis were observed. At the time of presentation, most patients had multifocal consolidation and the development of pleural effusion.[26] In a recent study based on postmortem findings of nine patients from India, it was observed that viral antigens were localized on the ciliated epithelium of the proximal airway. The virus proliferated in the upper respiratory tract and affected the lower respiratory tract indirectly through the release of inflammatory cytokines. The pathological findings in extrapulmonary organs were attributed to multiorgan dysfunction syndrome rather than a direct viral cytopathic effect. There was no evidence of transplacental transmission of virus from the mother to the fetus. Patients were prone to fungal and viral coinfections, as well as bacterial infections, depending upon their environment.

Secondary bacterial coinfection was the most frequent complication of influenza during the 1918 and 1957 influenza virus pandemics. The frequency of these bacterial coinfections has decreased in subsequent pandemics, especially the 2009 influenza A (H1N1) pandemic. Bacterial pneumonia was observed in 55% of cases, in comparison with 90% of 1918 pandemic autopsies and 75% of 1957 autopsies.[27] The decreased cases of bacterial pneumonia in 2009 influenza A (H1N1) can be attributed to better diagnosis, medical access and the availability of broader antimicrobial treatment.[28,29]

In the influenza pandemics of 1957 and 1968, clinical illness was mostly confined to the respiratory system, while the infections caused by the 1918 and the human H5N1 strains caused multisystem dysfunction and immune dysregulation. This suggests that highly pathogenic influenza viruses that directly adapt to humans are capable of causing a more severe and inappropriate immune response than reassortant viruses.[5]