Before the COVID pandemic, the World Health Organization (WHO) had made a list of priority infectious diseases. These diseases were seen as threats to global public health but required further research to improve their surveillance and diagnosis. In 2018, the term "disease X" was added to this list. It signified the possibility of an unknown pathogen emerging and causing a pandemic.
While it's one thing to acknowledge the limits of our knowledge about the microbial world, there is now more focus on how we can systematically prepare for future pandemic risks.
Former US Secretary of Defence Donald Rumsfeld once discussed the concept of “known knowns” (things we are aware of), “known unknowns” (things we know that we don’t fully understand), and “unknown unknowns” (things that are beyond our current awareness). Although his comments were made in the context of weapons of mass destruction, this framework can also be applied to understanding and addressing future pandemic threats.
Influenza: A ‘Known Known’
Influenza is an example of a “known known.” We experience minor outbreaks each winter, caused by small changes in the influenza virus. However, more significant changes in the virus can also occur, leading to widespread transmission in populations with little pre-existing immunity. The swine flu pandemic of 2009 is a recent example.
However, there are still many unknowns about influenza. For instance, we don't fully understand what drives these mutations, how they interact with population immunity, and how to predict the virus's transmission and severity each year.
Currently, the H5N1 subtype of avian influenza (commonly known as "bird flu") has spread widely around the globe. It has caused the deaths of millions of birds and has even spread to mammals, including cows in the United States and marine mammals in South America. Human cases have been reported in people who had close contact with infected animals. Fortunately, there is no evidence of sustained transmission between humans so far.
In a large country like Australia, detecting influenza in animals is a massive task. However, systems are in place to detect and respond to bird flu outbreaks in wildlife and farm animals. Despite this, future influenza pandemics are inevitable. It is also worth noting that while attention has long been focused on avian influenza, the 2009 pandemic originated from pigs in central Mexico, not birds.
Coronaviruses: An ‘Unknown Known’
Coronaviruses are more familiar than people might have realized before the COVID pandemic. We had already seen significant outbreaks caused by other coronaviruses, such as severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS). These are closely related to SARS-CoV-2, the virus that causes COVID-19.
Although these earlier coronaviruses faded from public attention, the WHO listed coronaviruses in 2015 as diseases with pandemic potential. Previous research on these viruses played a crucial role in the rapid development of COVID vaccines. For example, early work on a MERS vaccine by the Oxford group was instrumental in creating AstraZeneca's COVID vaccine. Similarly, prior studies on the coronavirus spike protein were critical in developing mRNA vaccines.
It seems likely that we will face future coronavirus pandemics. Even if they do not reach the scale of COVID, their impacts can still be significant. In 2015, a MERS outbreak in South Korea caused only 186 cases over two months, but the cost of controlling it was estimated to be USD 8 billion (AUD 11.6 billion).
The 25 Viral Families: Addressing ‘Known Unknowns’
Attention is now turning to the “known unknowns.” There are around 120 viruses from 25 families that are known to cause human diseases. Members of each family share similar properties, and our immune systems react to them in similar ways.
One example is the flavivirus family, which includes the well-known yellow fever and dengue viruses. Other important members of this family are Zika virus, which can cause birth defects if pregnant women are infected, and West Nile virus, which can lead to encephalitis, or inflammation of the brain.
To systematically address these threats, the WHO’s blueprint for epidemics considers different types of pathogens from various viral families. The aim is to expand our understanding of viruses by studying individual pathogens in each category.
The US National Institute of Allergy and Infectious Diseases has taken this a step further by preparing vaccines and therapies for prototype pathogens from key virus families. The goal is to use this knowledge to quickly develop vaccines and treatments for related viruses if a pandemic were to emerge.
Pathogen X: The ‘Unknown Unknown’
“Disease X” refers to the unknown unknowns, a pathogen that we have not encountered yet, but which has the potential to trigger a severe global epidemic. To prepare for this possibility, we need new forms of surveillance that look for where new pathogens might emerge.
There is growing recognition that we need to take a broader view of health. This perspective, known as "One Health," looks beyond human health and includes the health of animals and the environment. Factors such as climate change, intensive farming, the exotic animal trade, human encroachment into wildlife habitats, increased international travel, and urbanization all affect the emergence of new infectious diseases.
This approach also has implications for reducing the risk of pathogens “spilling over” from animals to humans. Targeted testing of animals and people who work closely with animals could help in early detection. Current testing focuses mainly on known viruses, but new technologies can be used to look for unknown viruses in patients with symptoms that suggest new infections.
We live in a world full of potential microbiological threats. While we have seen pandemics caused by influenza and coronaviruses in the past, a broader range of pathogens could still cause significant outbreaks in the future.
By continuing to monitor for new pathogens, improving our understanding of key virus families, and developing strategies to reduce the risk of spillover, we can effectively prepare for and reduce the likelihood of future pandemics.
