Tracing the origin of an epidemic is essential in understanding its source, how it spreads, and how to prevent further infection. This allows, for example, appropriately differing prevention implementation plans in rural and urban areas, safeguarding of healthcare professionals, and research into future prevention and treatments. Influenza, for example, is one of the most common infections across the globe. With recent devastating epidemics of Ebola, Zika and SARS, understanding the mechanisms of highly infectious contagion could facilitate policies for future epidemics and pandemics. Understanding the histories of past pandemics therefore form part of this research.
Spanish influenza infected 500 million people immediately after the First World War, killing up to 100 million – more than both World Wars combined. This is unusual in an influenza epidemic as, generally, host-pathogen interactions cause selection for restrained virulence; if the virus kills the host too quickly it would not have a chance to spread.
There are multiple theories for the evolutionary origin of Spanish Influenza. ‘Purulent bronchitis’ in which patients developing a blue facial hue, a characteristic symptom of Spanish flu, was reported as early as 1916 on the Western Front. There was also a small but severe flu outbreak in an army camp in Kansas in 1918, immediately preceding larger outbreaks identified as Spanish flu. It has even been suggested that a severe and unidentified respiratory disease epidemic in Shanxi province, China in late 1917 was brought to the Western Front by supplied workers and soldiers. This last theory, however, is weakened by genetic evidence for a relation between the Spanish flu virus and a North American bird flu strain.
The origins of past flu epidemics may provide insights into present day flu strains. The trenches’ conditions of close contact (which increase contagion) and high mortality (providing less time for viral multiplication) may have allowed the bypassing of this rule. In this case, the evolutionary path could feasibly cause selection for a highly contagious virus that multiplies rapidly without regard for the mortality of the host since they would be likely to die anyway. Additionally, its global spread will likely have been facilitated by the huge international demobilisation of troops back to all corners of the world.
Last year’s flu season (winter 2017-2018) was particularly severe, presenting as an old and virulent strain subtype, H3N2. The seasonal flu vaccine is produced using early forecasts but efficacy against the emergent season’s prominent strain remains between 30 and 60%. Last year’s H3N2 mutated more rapidly to evade the immune system and the vaccine’s antigens, therefore it reduced the flu vaccine’s efficacy even further. While flu is not likely to kill, it does reduce the immune system’s defences to allow opportunistic infection to cause higher rates of respiratory diseases than normal last year, mirroring the cause of Spanish Influenza’s high mortality rate. Other factors, such as reduced vaccination rates due to safety concerns and the increasing antibiotic resistance, increase rates of infection and reduce ability to treat patients.
However, the production of a universal vaccine is a real potential solution. Antigens in vaccines currently represent the variable regions of the viral coat specific to the strains predicted to be most prominent that season. This facilitates the immune system in building immunity through its natural defence mechanism so that it can then subsequently rapidly identify the strain upon infection. The problem lies in both the strain forecast being inaccurate (hundreds of strains emerge each season) and the variable region being under pressure from the hosts’ immune systems to change its shape. However, the non-variable region, or ‘stem’, shows promise for a universal vaccine and could allow the immune system to identify multiple strains rapidly, regardless of the variable regions changing. Alternatively, a vaccine containing a live but genetically engineered harmless viral strain could provide a more persistent immune response from the immune system.