A Perspective of Influenza Pandemics

Abstract

Abstract The dates of global influenza pandemics are well known as 1848, 1889, 1918, 1957, 1968 and 2009. Less well explored are the so‐called pseudopandemics of 1976 and 1977. Each of these pandemics uncovered a uniqueness either of the virus, the infection, the longevity of human protective immune memory or the scientific and community response. Thus, persons born before 1848 had long‐term immunity from a presumed infection with an H1N1 virus to protect them in 1918. Similarly, older persons were protected from the 2009 H1N1 pandemic because they had immunity from a variant of the (H1N1) virus circulating in the 1950s. Three of these pandemics had geographically different origins: the 1889 pandemic started in Russia, the 1918 outbreak possibly in France and the 2009 pandemic in Mexico. Little is known about the origin of the 1848 pandemic. These geographical observations do not perturb the published genetic analysis, which suggests Asian origins of both epidemic and pandemic viruses. Extra research is now directed towards Universal Influenza Vaccines, host proteins as targets for new inhibitory drugs and simple but possibly effective interventions using hygiene, cough etiquette and social distancing. Against all predictions we are still unable to deduce from total virus genome sequencing whether a newly emerged influenza virus will be extra virulent and indeed be able to spread from person to person. However, recent laboratory experiments have identified as few as four mutations of bird flu (H5N1), which potentially allow spread amongst animals and we can deduce and calculate that such mutants, at least with H5N1 virus, already exist in nature. It would be wise to revisit pandemic plans immediately and at the same time to increase surveillance at the interface between birds, pigs and humans where too few viruses are analysed. The World Health Organization has published new guidance and plannings. In the author's opinion it is quite possible that the next pandemic could arise as early as 2018, the anniversary of the Great Spanish Pandemic of 1918 and it would be sensible to have such a date as a target for completeness of pandemic plans. Key Concepts: The scientific community is continually revisiting the 1918 pandemic to estimate mortality (now revised upwards and approaching 100 million) and also the genetic determinants of virulence. The extensive postmortem lung samples of 1918 patients in pathology museums in the USA and England, exceeding those of all subsequent pandemics are important for this research. As with the 1918 pandemic, the global mortality figures of the influenza A (H1N1) pdm09 pandemic have been reestimated upwards from approximately 18 000–575 500. New studies of bird influenza (H5N1) show that only four mutations could allow this avian pathogen to spread between mammals and hence by deduction to evolve into a significant human pathogen. Pandemics can start anywhere in the world, although generation of genetic diversity is highest in the tropical regions of the world. Such viruses move in travelling individuals, mainly by aeroplane to the two ‘sinks’ of the Northern and Southern Hemisphere. Spread of old and new pandemic viruses in the community is governed by Darwin's evolutionary theory of ‘Survival of the Fittest’ whereby ‘new’ viruses, to which no person has immunity, have the greatest potential to spread. The lung pathology of victims is remarkably similar in pandemics of 1918, 1957, 1968 and 2009. In each pandemic there was a high incidence of coinfections with bacteria. Preparation for the next pandemic, including stockpiling of antibiotics, antivirals, pneumococcus vaccines and influenza vaccines to influenza A (H5N1), (H2N2) and (H7N9) is underway. Pandemic plans need to be updated continually and to have flexibility to cope with virus virulence ranging from mild to severe. Such plans in large corporations, for example, are being tested in the USA at the present time. WHO has recently issued a new guidance for countries ‘pandemic influenza risk management’. A new generation of universal influenza vaccines, broad spectrum antivirals and rapid molecular diagnostics will assist during a new pandemic. Pandemic virus surveillance at the interface between birds, animals and humans is extremely sparse globally given that domestic chickens outnumber humans by three to one. There needs to be a huge expansion in this important endeavour. The proper use of hand hygiene, cough etiquette and personal social distancing has been a focus of recent attention.