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

Origin & Epidemiology

It is necessary to look to history in order to understand the genesis of influenza pandemics. The genetic sequencing of the 1918 virus suggests that it was an avian influenza virus strain that adapted itself to humans.[3] The phylogenetic analysis of the HA and NA genes support the fact that the precursor virus had not circulated in human or swine population in the few decades immediately before the start of the 1918 pandemic.[7]

The striking feature of the 1918 pandemic was that it was the first time that both pigs and humans were infected simultaneously with an avian-like influenza virus.[2,8] In contrast with interpandemic seasonal influenza, where the majority of influenza-related deaths occur in the elderly, the pandemic periods witness a marked mortality age shift towards a younger population. The age shift during the 1918 pandemic was extreme, in which the majority of deaths occurred amongst persons under 45 years of age, sparing people above this age.[9] The most significant pattern in the epidemiology of the 1918 pandemic was the unusual W-shaped mortality pattern peculiarly associated with an overwhelming number of deaths in young adults between 20 and 40 years of age.[5] 'Antigen recycling' is a phenomenon by which exposure to influenza antigen in childhood results in lifelong protection, and results in mortality sparing in seniors when a similar antigen emerges many years later. This might explain the pandemic age shift to younger age groups, which was also consistent with the recent A(H1N1)pdm09, with a mean age of influenza-related deaths of approximately 30–42 years compared with approximately 77 years in the interpandemic season. Chowell et al. reported a herald pandemic wave with elevated mortality in young adults that was similar to the USA and Europe.[10] The mortality rates reflected the fact that even Mexican seniors ≥65 years of age were not spared, and experienced influenza-related excess mortality that was in contrast to that of the USA and Europe. The 'first wave' of the 1918 pandemic arose in the USA in March 1918. However, it is difficult to assign a geographical point of origin due to the simultaneous appearance of influenza in March–April 1918 in North America, Europe and Asia. The 'second wave', or main wave, occurred in September–November 1918. In many places there was a severe third wave of influenza in early 1919.[11] The pattern of the 1918 pandemic waves was not universal, and data from New York City suggested pre-pandemic activity before the spring of 1918, with an impact that was far from mild.[12]

After its emergence in North America, the 2009 pandemic influenza virus spread rapidly throughout the world. In contrast with the 1918 H1N1 influenza virus, the 2009 H1N1 strain was generated by reassortment between two well-established swine influenza lineages, and was a highly virulent amalgam of swine, human and avian influenza genes (Figure 1).[13] The NA and M genes were derived from the Eurasian swine genetic lineage. The HA, NP and NS gene segments were derived from the classical swine lineage. The PB1, PB2 and PA gene segments were contributed by the swine triple-reassortant lineage.[14] Compared with past influenza pandemics, the median reproduction number during the 2009 pandemic was similar to the 1968 pandemic, or slightly smaller than that of 1918 or 1957.[15] In a study involving 11 countries, it was observed that, in 2009, approximately 75% of the confirmed cases were below 30 years of age, with a modest peak at the 10–19 age group. Fewer than 3% of the cases were in individuals ≥65 years of age. The drop in incidence after age 20 was marked and uniform.[16] The phenomenon known as 'senior sparing' was observed in age cohorts born prior to the 1957 pandemic. It is consistent with first exposure to antigenically-related A/H1N1 viruses in childhood, a pattern consistent with the 'antigen recycling' and 'original antigenic sin' hypotheses.[17]

Figure 1.

Reassortment in influenza A virus from 1990 to 2009.

The A(H1N1)pdm09 waves varied substantially in number and intensity across the globe. Chowell et al. reported the occurrence of a 'herald' pandemic wave in the spring of 2009 in Mexico, the USA and the UK, followed by one or more waves during the summer and fall of 2009.[18] The southern hemisphere experienced only a single pandemic wave in 2009. Other countries in Europe also experienced a single main wave in the fall of 2009, followed by a recrudescence of H1N1 activity more than a year later in winter 2010–2011. Their study also supports the effectiveness of early mitigation efforts and cancellation of large public gatherings, including the closure of schools. Mexico experienced three pandemic waves of A(H1N1)pdm09, associated with higher excess mortality rates than those reported in other countries. A recrudescent wave began in Mexico in December 2011, following a 2-year period of sporadic transmission. A substantial change in the age distribution of cases and deaths from December 2011 to February 2012 was observed in Mexico compared with A(H1N1)pdm09. In 2011–2012, there was a significantly higher proportion of hospitalization of laboratory-confirmed A/H1N1 individuals older than 60 years. There was also a reduction in the proportion of A/H1N1-positive hospitalizations among school-age children compared with the 2009 pandemic. The age shift observed in the 2011–2012 winter season could be attributed to the emergence of a drift variant A/H1N1 and/or the buildup of immunity among younger patients.[17]