A Conversation About Pandemic Preparedness – Part 1

Professor Benjamin J. Cowling. Photo courtesy of The University of Hong Kong

I recently spoke with Professor Benjamin J. Cowling about influenza pandemic prevention and preparedness.

Our conversation will be posted in two parts. The first part below is about pandemic preparedness and genomics. The second part (to be posted next week) will examine national and global responses.

Professor Cowling is Division Head at the Division of Epidemiology and Biostatistics at the School of Public Health (SPH) at Hong Kong University.

Hong Kong is interesting because it is often considered to be one of the epicenters of influenza pandemics.

About Professor Cowling:

• He holds a PhD in medical statistics from the University of Warwick, has conducted postdoctoral work at Imperial College, London and has been the Head of the Division of Epidemiology and Biostatistics at SPH since 2013.
• He is also co-Director of the World Health Organization (WHO) Collaborating Centre for Infectious Disease Epidemiology and Control at SPH.
• His research is focused on infectious disease epidemiology. He has designed and carried out large community-based studies of influenza transmission and the effectiveness and impact of control measures. Recently, he has looked at respiratory virus transmission, influenza vaccination effectiveness, immunity to infections, and the potential causes and the interferences between respiratory viruses. He works closely with China’s Centers for Disease Control and Harvard University’s Center for Communicable Disease Dynamics.
• Professor Cowling is a Fellow of the Royal Statistical Society and a Fellow of the UK Faculty of Public Health. He is also Editor-in-Chief of “Influenza and Other Respiratory Viruses”, an Associate Editor of “Emerging Infectious Diseases”, a Section Editor of “PLOS ONE”, and founding editor of “PLOS Currents: Outbreaks”.
• He has 350 publications and has received numerous awards including a Croucher Senior Research Fellowship, HKU Outstanding Researcher Award, HKU Outstanding Young Researcher Award, and American Journal of Epidemiology (AJE) Article of the Year 2014.

Q: Prof. Cowling, could you please elaborate on pandemic preparedness? How can a country prepare for a pandemic or an outbreak?

Prof. Cowling: There are different kinds of pandemics. As far as influenza pandemics go, a lot of efforts have taken place over the past 20 years, starting in 1997 when avian influenza A subtype H5N1¹ was first identified as a serious threat. Ever since then, countries have been thinking about how best to prepare and respond. The World Health Organization (WHO) is involved in advising countries in this respect.

There have been three big areas of investigation over this period: (1) vaccine development and production; (2) antivirals; and (3) non-pharmaceutical interventions.

The most important efforts have been in the vaccine area. We are now able to develop a vaccine against a new influenza virus within about 5-6 months, which is an improvement as compared to what was available 20 years ago. Vaccine companies have played a large role here, though WHO has assisted by putting the mechanisms in place to help rapidly identify new pandemic viruses. In particular, the WHO has done a lot to streamline the process of developing “vaccine seeds” – i.e. create and characterize viruses that can be used by vaccine companies to produce and manufacture vaccines. While I’m not certain about specific current global manufacturing capacity, I believe more than 500 million doses, and perhaps even up to 1 billion doses, of pandemic vaccine could be made fairly quickly.

As for antiviral medications, WHO has been somewhat cautious about recommending countries stockpile them. The main antiviral for flu is oseltamivir (“Tamiflu”). Some countries have quite large stockpiles of Tamiflu, while others have decided not to do so. There has been some controversy over how effective Tamiflu is. During the 2009 influenza pandemic, the UK dispensed a lot of Tamiflu via a telephone hotline under the “National Pandemic Flu Service”. They continue to stockpile large amounts of it in preparation for the next pandemic. Most other countries haven’t done that, though Japan is a big user of Tamiflu for seasonal flu. This year, there are several new antivirals available and countries are deciding the extent to which they should stockpile them.

The third big development involves non-pharmaceutical interventions. These are non-drug, non-vaccine measures. WHO and individual countries have been looking at what might be possible and effective in the event of another pandemic. I have done a lot of work in this area and am currently working with WHO to update their non-pharmaceutical intervention guidelines. These include facemasks, advice on handwashing, and “social distancing” measures – e.g. if people are sick, we ask them to stay home, we close schools, workplaces, public areas, shopping malls, etc. At a high level, decisions need to be made on travel reductions or restrictions, or even border closures.

Border closures are, for most countries, not really feasible. There are a few places in the world, such as some Pacific islands, where one could imagine some kind of serious effort to prevent people from coming in while still keeping trade going. But preventing the movement of people would be pretty drastic.

So those three, the vaccines, the antivirals and the non-pharmaceutical interventions, are really important. WHO also provides guidance to countries on how to prepare and use these interventions.

For other pandemics, WHO has a role to play but they haven’t so far been too active. They are worried about local and regional epidemics such as Ebola, Zika and Yellow Fever. But they are not specifically concerned that those will cause highly global catastrophes. Influenza is the one pathogen that they have been seriously concerned about in that respect. In general, these other pathogens pose more localized risks which can be controlled regionally. Zika, however, shocked the global health community because suddenly it was everywhere. No one had really been looking out for it – and then suddenly there was a report from Brazil and it turned out it has been all around the world already. Fortunately, it was not as dangerous as some of the early reports had suggested.

Q: Is there a way to make people less susceptible to viruses with the use of genomics? Is there genetic research being done to consider why some people do not get as sick as others?

Prof. Cowling: That is a really interesting question. Why do some people seem to be more vulnerable than others? There is not a lot of evidence on why that might be. One might think that differences in human genetics could explain this, but when we look at different parts of the world, different racial groups for example, there are no obvious major differences.

There is one gene, called IFITM3², and there have been a few papers that describe differences in severity in Europe and Asia based on the prevalence of that gene, but I would say the evidence for that is still somewhat limited. I certainly think we need more studies in this area, and I’m surprised those have not really been done yet. If you search for IFITM3 in the medical literature, you will find only a few papers.

But even if we could determine that a gene like IFITM3 were responsible for some part of severity outcome, it’s not clear we could do much about it. I don’t think we have the tools to modify peoples’ genes. And I would say also that modifying them to make people less susceptible to flu might have other consequences that we haven’t realized, because we know there are interactions between the strength of immunity and autoimmune diseases. For example, if you make people’s immune systems stronger maybe you would make them then also more vulnerable to autoimmune diseases that are common in older people.

Part II of this conversation will be posted next week. Stay tuned!

1. The Asian H5N1 virus was first detected in Guangdong Province , China, in 1996, when it killed some geese, but it received little attention until it spread through live-poultry markets in Hong Kong to humans in May 1997, killing 6 of 18 infected people. From 1997 to May 2005, H5N1 viruses were largely confined to Southeast Asia, but after they had infected wild birds in Qinghai Lake, China, they rapidly spread westward. The intermittent spread to humans will continue, and the virus will continue to evolve. Global spread of H5N1 – Wikipedia en.wikipedia.org/wiki/Global_spread_of_H5N1

2. From NCBI Gene: The protein encoded by this gene is an interferon-induced membrane protein that helps confer immunity to influenza A H1N1 virus, West Nile virus, and dengue virus. Two transcript variants, only one of them protein-coding, have been found for this gene. IFITM3 gene – Genetics Home Reference – NIH ghr.nlm.nih.gov/gene/IFITM3