How to be ready for the next influenza pandemic

Abstract

This year marks the 100th anniversary of the 1918 influenza pandemic, the worst acute infectious disease outbreak in modern history. The pandemic was caused by influenza virus H1N1 and emerged in the final stages of World War 1. It is estimated that between 20 million and 50 million people died during this pandemic, with a uniquely high mortality in young adults aged between 20 and 40 years. Low-income countries were hit particularly hard (17 million people are thought to have died in India alone) because of their poor health systems. Why the 1918 pandemic was so severe is still a matter of debate, but immunological factors and secondary bacterial infections were major contributors to the heavy death toll. Other influenza pandemics, albeit less severe, have then occurred in 1957, 1968, and 2009, so a new one appears inevitable at some point in the future. Thus, on the centenary of the 1918 pandemic, it is timely to ask ourselves whether the world would be prepared now for such an event. The answer sadly is no: we do not know what virus will cause the next pandemic, there is no way to rapidly develop and deploy an effective vaccine against a pandemic virus, differences in quality of health systems hamper a prompt response, and surveillance data on influenza have major gaps. At the Massachusetts Medical Society's annual meeting on April 27, American philanthropist Bill Gates presented a simulation by the Institute for Disease Modeling that found that a new influenza virus like the one that caused the 1918 pandemic would now most likely kill 30 million people within 6 months. Thus, an influenza pandemic represents a real threat that could only be managed with a rapid and effective response from both national governments and the international health community, something that was not seen for the most recent major oubreak of a deadly infectious disease, the emergence of Ebola virus disease in west Africa in 2014-16. In order to improve the preparedness of the global health community to a pandemic, three areas are crucial: vaccination, surveillance, and building response capacity. As discussed in our May Editorial, the development of a universal influenza vaccine, the holy grail of influenza research, would enhance the capacity to protect people from infection. Gates' announcement of a US$12 million donation to contribute to the development of such a vaccine is therefore welcome news. However, the development of an effective vaccine is expected to take at least 5–10 years. Surveillance for influenza is of crucial importance but is also complex because it needs to cover two key populations: animals and humans. It is expected that the next pandemic influenza virus will originate from a spillover from birds, the natural reservoir of all influenza viruses, or pigs, in which avian and human viruses can coexist, thus favouring recombination. At the recent ECCMID meeting, Colin Russell presented the results of a study that mapped areas in the world at highest risk of spillover of avian and swine influenza virus into humans. Particularly ominous was the observation that surveillance for viruses circulating in birds and pigs in such areas is often very limited, so the rapid spread of an influenza virus of pandemic potential could easily go undetected. Equally patchy is the surveillance of human cases of influenza, which is essential to recognise unusual severity or incidence of cases which can be a prodrome for a pandemic. WHO has conducted monitoring through the Global Influenza Surveillance and Response System for over half a century, relying on collection and preliminary analysis of virus specimens from national influenza centres. Not all countries have such centres (for example, only 18 African countries have one) so the reporting of influenza cases remains suboptimum. In case of an influenza pandemic, the capacity to respond promptly will play a key part because of airborne transmission. Antivirals and antibiotics to prevent secondary bacterial infections will be important, while awaiting development of an effective vaccine, but stockpiles of these are currently insufficient. Moreover, there is need to invest in strengthening health systems and microbiological capacities on the ground to enhance the rapid response to any outbreak. Influenza is the infectious disease with a proven record of causing pandemics, so it is essential that it remains at the centre of efforts for pandemic preparedness. The next influenza pandemic will be a real test for the international health community. We should not find ourselves unprepared—to be so could cost millions of lives. For more on historical recommendations of influena surveillance see Editorial Lancet 1958; 7025: 833–35 For more on historical recommendations of influena surveillance see Editorial Lancet 1958; 7025: 833–35