History of Clinical Developments for Different Influenza Outbreaks

History of Clinical Trials During Different Influenza Epidemics

Despite its severity, COVID-19 is by no means an isolated event in history. For centuries, influenza and other viruses have plagued societies across the globe – and important lessons can be learned from these events. Influenza A viruses, through multiple mutations, were responsible for four major pandemics from 1918 to 2009, namely the Spanish flu (H1N1), Asian Flu (H2N2), Hong Kong flu (H3N2), and swine flu (H1N1).

Given the urgent need to slow the COVID-19 virus and its mutations, it is useful to re-examine previous pandemics, their severity, and the subsequent clinical efforts to produce an effective vaccine.

The Spanish Flu of 1918 (H1N1)

By far the worst recorded influenza pandemic, the Spanish Flu killed an estimated 50 million people, roughly 3 percent of the world’s population at that time. Peaking around the end of World War I, the disease found fertile ground in war-torn Europe and abroad, aided in large part by massive population movements such as civilian refugees and soldiers on the move.

Initially, medical experts did not know the causes of H1N1, and there was no effective treatment for a disease that showed exceptional virulence and transmission. In time, it was generally understood that a blood transfusion from a survivor would be an effective treatment, but the overall science of blood transfusion itself was still in its infancy.

The Spanish Flu was a catalyst for research, which led to scientists finally proving that influenza was caused by a submicroscopic infectious agent and not a bacteria. This development revolutionized the field of virus research generally.

By 1931, researchers at Vanderbilt University found ways to grow the influenza virus in fertile chicken eggs. By the late 1930s, they began to work on a vaccine – already understood to be the ideal method of dealing with pandemics.

The Asian Flu of 1957 (H2N2) 

The Asian Flu of 1957 was a Category 2 flu pandemic that originated in China in early 1956. It lasted until 1958, when a second wave eventually petered out and the virus turned into a seasonal flu. The disease originated from a mutation in wild ducks, combined with an existing human strain.

H2N2 quickly spread, killing over 2 million people globally. Still, the Asian Flu gave rise to a large-scale vaccine implementation program whose effectiveness was clear to see, turning this deadly disease into one of the least severe influenza pandemics of the 20th century. The rapid development of a working vaccine saved millions of people from infection, while advancements in antibiotics helped with secondary infections and reduced the overall mortality rate still further.

The Asian Flu also shed light on how some viruses range in susceptibility and duration across populations, with scientists beginning to understand why some sick people present few symptoms while others deteriorate quickly. Clinical research led to new insights about asymptomatic carriers, as well as advancements in vaccine development. The lessons learned in these areas would go on to save countless lives.

The Hong Kong Flu of 1968 (H3N2)

The Hong Kong Flu was caused by an influenza A (H3N2) virus composed of two genes from an avian influenza A virus, including a new H3 hemagglutinin, as well as the N2 neuraminidase from the 1957 H2N2 virus.

Despite the recent Asian Flu of 1957, few cohesive pandemic plans had been put into place globally in the intervening years. H3N2 was therefore able to kill over 1 million before it became a seasonal flu. Researchers from Hong Kong, Japan, and elsewhere around the world scrambled to produce an effective vaccine to protect against H3N2, a disease which was often fatal to those over 65.

While the body count remained fairly low compared to previous pandemics, H3N2’s increased influenza morbidity and mortality heralded more severe annual epidemics of seasonal flu than had been seen previously. Despite the lack of preparation for this pandemic, research from the Asian Flu led to more rapid developments in treatment as well as more effective prevention techniques.

The Swine Flu of 2009 (H1N1)

The Swine Flu virus was first identified in Mexico in April 2009, and was named for its similarity to flu viruses that affect pigs. With decades having passed between pandemics, most young people did not have any immunity to this disease, allowing H1N1 to spread rapidly. Unlike many previous pandemics, this one seemed to affect children more than the elderly, many of whom already had some immunity to related strains.

Due to advancements in pandemic protocol, information sharing, vaccine implementation, and immunity among the elderly, H1N1’s infection rate and mortality were significantly milder than predicted. Today, it is a seasonal flu that circulates each winter – but at the outset it significantly affected an entire generation that had never experienced a pandemic before.

Future Outbreaks

Previous outbreaks have proven to be invaluable to researchers by showing how preparation, cooperation, and vaccine implementation can stop global pandemics when they are still outbreaks. Every generation faces waning immunity from previous viruses, so the cyclical nature of pandemics may be unavoidable. Each major outbreak causes immense human suffering, but is also an opportunity to advance medical knowledge and improve preparation to minimize impact.

Clinixir is at the forefront of this clinical development effort, working alongside our valued pharmaceutical partners to apply these important lessons from the past. Contact us today to get started.


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