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

Abstract and Introduction


The 2009 influenza pandemic A(H1N1)pdm09 of swine origin and the continued circulation of highly pathogenic avian H5N1 strain in humans are stark reminders of the unpredictable nature of the influenza virus. Experiences from the 1918 and 20th century influenza pandemics helped immensely in the preparation of a better response for A(H1N1)pdm09. The explosive pattern of the 1918 pandemic makes it a benchmark for pandemic planning and preparedness today. Its similarities with the 2009 pandemic makes it even more intriguing, and it is a great surprise that the two strains, separated by a period of 91 years, share such similar features. This review is an attempt to summarize the literature describing the important features of the 1918 and 2009 pandemics. This may provide a better understanding for the early detection and control of influenza pandemics in the future.


The 20th century witnessed three influenza pandemics: the Spanish Flu (1918, H1N1), Asian Flu (1957, H2N2) and the Hong Kong Flu (1968, H3N2). Influenza pandemics are initiated by the introduction and successful adaption of a new virus subtype with a novel hemagglutinin (HA; or novel HA and neuraminidase [NA]) that is immunologically distinct from previously circulating strains.[1] The new virus subtype may arise by either of two mechanisms: by the direct transmission of animal influenza strains to humans, as happened in 1918 with the 'Spanish influenza' (H1N1); or through reassortment between human and animal influenza virus, as occurred in 1957 with the 'Asian influenza' (H2N2), and again in 1968 with the 'Hong Kong influenza' (H3N2) (Table 1).

The 1918 Spanish flu killed an estimated 50–100 million people worldwide, and has been aptly referred to as 'the mother of all pandemics'.[2] The pandemic strain of 1918 could not be isolated during the pandemic period, but the molecular secrets behind its high virulence were revealed once the virus was reconstructed using reverse genetics technology on RNA from the lungs of several victims.[3]

As stated above, the influenza pandemic of 1957 was caused by the Asian influenza A (H2N2) strain, and the Hong Kong influenza A (H3N2) strain caused the 1968 pandemic. The two pandemics claimed approximately 500,000–2,000,000 human lives.[4] Both of these reassortant pandemic virus strains emerged in China and included a combination of avian and human viral genes.[5]

In 1997, 18 cases of avian influenza A H5N1 infection occurred in humans in Hong Kong. It soon became evident that the avian influenza virus H5N1 could cross the species barrier and infect humans. Since then, extensive outbreaks of avian H5N1 infections with sporadic human spread have been occurring in various countries. H5N1 influenza virus had previously not been isolated from humans, raising concern over the possibility of an upcoming influenza pandemic. The human H5N1 virus was not a reassortant like the 1957 and 1968 pandemic strains; instead, all of the viral genes originated from avian virus.[6]

The influenza virus resurrected itself again in March–April 2009, when a novel strain was isolated from humans in Mexico and the USA, followed by a worldwide spread across 214 countries, causing approximately 500,000–1,000,000 deaths. In August 2010, the WHO declared the end of phase six of this influenza pandemic, and the beginning of the post-pandemic period. In the post-pandemic period, the H1N1 2009 virus demonstrated the attributes of a seasonal influenza virus and may continue to circulate for years to come.[101] A/California/7/2009 (H1N1) pdm09-like virus has been included in the vaccine strain for the year 2012–2013, indicating its continued circulation around the world.[102] The 2009 pandemic strain shares striking similarities with the 1918 pandemic virus, and their in-depth analysis may solve many mysteries surrounding the 2009 pandemic (Table 2).