This week, the WHO unveiled its new Global Influenza Strategy for 2019-2030. WHO Director-General Dr. Tedros astutely noted, “The threat of pandemic influenza is ever-present” and expressed a need for additional efforts on a national and global levels to improve preparedness for both seasonal and pandemic influenza. Outbreak Observatory has addressed seasonal influenza in a number of previous Outbreak Thursday posts as well as our first observation to Taiwan, but this week, we will take a brief look at pandemic influenza and the new WHO global strategy.

Pandemic Influenza

There are several key distinctions between pandemic and seasonal influenza in terms of the virus, transmission pattern, and overall impact. Seasonal influenza occurs every year, without fail, typically during the winter months, and it evolves steadily from year to year, commonly referred to as antigenic drift. This slow evolution means it remains largely familiar to the human population (and our immune systems). This means individuals retain some immunity from exposure during previous seasons. We can also anticipate to some degree which strains to expect in the upcoming season, which enables us to develop vaccines to combat the most likely strains of the virus. Conversely, pandemic strains may evolve much more rapidly—eg, via antigenic shift, particularly when circulating in animal populations. These major changes may result in a strain of the virus that is novel to human populations. When humans face a newly emerging or re-emerging strain of influenza, there is very little natural immunity, and there may not be any vaccine immediately available that is effective against that particular strain (antivirals may also be less effective). Additionally, pandemic strains often cause severe disease in normal, healthy adults, whereas seasonal influenza is often more severe in vulnerable populations such as young children, elderly individuals, pregnant women, and those with chronic health conditions. The combination of these factors makes pandemic influenza strains particularly dangerous, as they can spread rapidly with very few tools available to interrupt or slow transmission or to treat infected individuals.

There have been 4 widely recognized influenza pandemics in “modern” history. Most recently, the world faced a re-emergence of H1N1 influenza A in 2009, a novel strain of a virus with a storied history. The US CDC estimates that the 2009 H1N1 pandemic resulted in nearly 61 million cases and 12,500 deaths in the US and between 151,700 and 575,400 global deaths. An estimated 80 percent of cases were in individuals under the age of 65 (compared to 70-90% over the age of 65 for seasonal influenza). In 1968, a novel strain of H3N2 influenza A emerged, a combination of a new H3 hemagglutinin and the N2 neuraminidase from the previous pandemic, H2N2 in 1957. The 1968 pandemic resulted in approximately 100,000 deaths in the US and 1 million globally. The 1957 H2N2 influenza A pandemic caused similar results, an estimated 116,000 deaths in the US and 1.1 million worldwide. The 1918 pandemic, also caused by an H1N1 influenza virus, is widely recognized as one of the most severe health events ever faced by the human race, responsible for somewhere on the order of 500 million cases—approximately one-third of the entire planet—and 50 million deaths. Some even estimate the death toll closer to 100 million.

WHO’s Global Influenza Strategy

The WHO’s Global Influenza Strategy (2019-2030) is guided by two primary goals: (1) developing improved tools for prevention, detection, control, and treatment of influenza; and (2) building and maintaining national-level prevention, surveillance, preparedness, and response capacity. These may seem similar, but there are some key aspects that differentiate them. The first pillar focuses on the availability of response tools, including antivirals and vaccines. As noted above, we may not have antivirals or vaccines available immediately to combat pandemic strains of influenza. The US and other countries maintain stockpiles of “pandemic influenza” vaccines, based on the strains evaluated as the most likely to cause a pandemic; however, these are in limited supply and may not necessarily be effective against the particular pandemic strain that emerges. With respect to seasonal influenza, this include advances such as universal influenza vaccine, the pinnacle of influenza vaccine research. The second principle largely refers to national-level programs, including influenza-specific policies and protocols. The WHO emphasizes that these national programs and policies collectively contribute to global health security, and it calls on every country to develop and implement these programs.

This is not the WHO’s first effort to coordinate global attention and efforts around influenza. In 2005, it published the Global Influenza Preparedness Plan, which expanded upon previous iterations to include the “prolonged existence of an influenza virus of pandemic potential,” such as the H5N1 strains that emerged in bird populations several years prior, and response to the simultaneous occurrence of multiple pandemic threats. It also updated the risk phase definitions for emerging pandemics. This was followed by the Strategic Action Plan for Pandemic Influenza in 2006, a plan that highlighted the role of regional collaboration to improve preparedness and response capacity for influenza pandemics in the near term as well as longer-term efforts to build global preparedness capacity, which would also support readiness for emerging infectious diseases with pandemic potential. Other efforts focused on specific aspects of influenza preparedness, such as the Global Action Plan for Influenza Vaccines, a 10-year program that aimed to reduce seasonal and pandemic vaccine shortages through developing sustainable vaccine production capacity, increase rapid vaccine production capabilities for pandemic vaccines (2 billion vaccines within 6 months of a vaccine prototype), and advancing technology to improve vaccine effectiveness. WHO regional offices have also published their own guidance, such as the Eastern Mediterranean Regional Strategy on Preparedness and Response for Human Pandemic Influenza. The WHO has also made a number of more recent efforts as well to address particular aspects of pandemic influenza preparedness, including for risk assessment and mitigation, developing national pandemic influenza plans, and conducting pandemic influenza exercises. Perhaps the most widely recognized document is the Pandemic Influenza Preparedness (PIP) Framework, published in 2011. The PIP Framework outlined international policies to ensure the rapid and equitable sharing of biological specimens and access to associated data, pharmaceuticals (including vaccines), and other benefits during an influenza pandemic.

The new global strategy takes a more holistic approach, addressing a broad scope of challenges, including vaccine and diagnostic development, disease surveillance, data analytics and modeling, animal health and zoonotic transmission, and international response coordination. The strategy outlines a series of Strategic Objectives, each with associated concrete actions; the role of the WHO in supporting these activities; and their relationship to other WHO programs and assets. The plan addresses both seasonal and pandemic influenza, as many aspects of preparedness and response activities will overlap between the two. And it warms our collective Outbreak Observatory heart to see the WHO explicitly note the importance operational research during outbreaks, including the need to identify optimal strategies for utilizing existing and future countermeasures. In fact, many of Outbreak Observatory’s principal areas of focus are included in this strategy, such as disease surveillance, risk communication, non-pharmaceutical interventions, and medical countermeasures distribution and dispensing. The WHO also includes enhanced data analysis, modeling, and forecasting efforts, to help better understand the impact of seasonal influenza and, ideally, predict the next influenza pandemic.

Beyond Influenza

Of all the pathogens with pandemic potential, influenza probably receives the most attention from a planning and preparedness perspective. Humanity has historical experience with several influenza pandemics over the past century or so, but it is far from the only threat. The emergence of coronaviruses, including SARS and MERS that have demonstrated the ability for human-to-human transmission, are a major threat. SARS cases were reported in more than 25 countries across 5 continents in 2003-04, and the 2015 MERS outbreak in South Korea demonstrated the ability of these viruses to rapidly spread around the globe. The emergence of Zika virus in the Americas in 2015 illustrated that even vectorborne diseases could have pandemic potential. Nipah virus recently emerged in western India, more than 1,000 miles from the nearest recorded outbreak, and the geographic range of the bats thought to carry henipaviruses spans South and Southeast Asia, northern Australia and Oceania, and most of Africa. There may also be a range of pathogens that we are not yet considering. Disease X, as designated by the WHO, or Clade X, as used in a recent Center for Health Security tabletop exercise, could pose major threats, particularly if no effective medical countermeasures (eg, treatments, vaccines) exist.

Conclusion

While the new WHO strategy specifically references influenza, many of the capabilities it aims to develop would also be critical in response to other pandemics, including for diseases that have not yet emerged. In fact, one of the key lessons from Clade X was that the capability to rapidly develop and manufacture vaccines and diagnostics for novel pathogens is a critical tool that does not yet exist. We are fairly adept at developing new influenza vaccines because we do it every year, but even then, the process takes months. Conversely, this capability does not exist at all for many other pathogens, or at least not on the scale necessary for a pandemic response. It is important to remember that influenza is not the only pandemic threat and that these capabilities support global health security more broadly.

As Dr. Tedros noted, the world is more prepared than ever to face health emergencies like pandemics, but these efforts are still not enough. As the old adage goes, “diseases don’t recognize borders,” and it will take a global effort to establish and maintain a collective, robust capacity to detect, respond to, and recover from pandemic threats such as influenza. The impact of the WHO global plan will certainly come down to implementation on a global level, including sufficient funding as well as political and social will, but the priorities identified and steps outlined will hopefully be an important first step toward focusing global efforts on this persistent threat.


Outbreak Observatory aims to collect information on challenges and solutions associated with outbreak response and share it broadly to allow others to learn from these experiences in order to improve global outbreak response capabilities.