During the first week of May (2009) The World Health Organization called an H1N1 influenza pandemic "imminent." The largest pandemic on record, the 1918 Spanish flu, spread to nearly every corner of the world and killed as many as 100 million people. Today, we are more capable of dealing with flu, but because of global interconnectedness, we're more capable of spreading communicable diseases as well.
Are governments treating the current flu with enough urgency? Too little? Too much? More importantly, if we have indeed entered a new "Age of Pandemics" (as the Wall Street Journal announced on May 2nd) what can we do to better prepare for the epidemics of the future?
We turned to Daniel J. Barnett , M.D., M.P.H., assistant professor in the department of environmental health sciences at the Johns Hopkins Bloomberg School of Public Health, and Tyler Kokjohn, professor of microbiology at Midwestern University and author of the "In The Shadow of Pandemic" to parse the future of flu. (May 4, 2009)
Interview by Rick Docksai
THE FUTURIST: According to the U.S. Centers for Disease Control, a fully evolved pandemic of a highly lethal flu strain (not H1N1 necessarily) could result in 134 to 233 million outpatient hospital visits and 1.5 to 5.2 million hospital admissions, as well as billions of dollars of revenue and GDP loss. Two years ago, the United Nations estimated that a human influenza pandemic of the H5N1, or bird flu strain, might result in a catastrophic 150 million deaths. Swine flu appears to be spreading faster, but it also appears less lethal. Do you have any sense of how many deaths might result from a swine flu pandemic? What's the worst case scenario for the U.S.? For developing nations? What’s the most likely scenario?
Daniel Barnett: It’s really difficult to say. We don’t know yet if the current strain may mutate into something more severe or something less severe. Based on recent genetic analysis of the strain, there are some potentially reassuring signs it may be relatively mild in comparison to past pandemic strains. But we don’t know how or if it will mutate in the coming weeks or months. That’s why it’s so critical for surveillance activities to be going on around the world and for agencies at the federal, provincial, and local levels to be in close communication.
THE FUTURIST: So cooperation among government agencies at all levels is a key component of the solution.
Barnett: Correct. More cooperation, and especially more local cooperation, is essential. Local-level responders know their jurisdictions best and are best-equipped to make tailored decisions to meet their local needs with guidance from the federal and state levels. For example, some districts in the U.S. have opted to close their schools for the time being; some have not. Jurisdictions are looking at their local situations and making tailored decisions accordingly.
I can’t overemphasize the importance of local response to this international crisis.
THE FUTURIST: In a 2006 article in THE FUTURIST, you judged vaccination to be “the ideal response” to an influenza pandemic. How ready are most countries to vaccinate their populations against swine flu? What could they be doing now to increase their readiness?
Barnett: The challenges with vaccine production relate to the technology that’s available, the resources that are available, and the time it takes to ramp up production of a vaccine tailored to a given influenza strain. Vaccination is the ideal approach, but it’s not realistically feasible in the short term.
The standard means of producing flu vaccines today is egg-based production using hens’ eggs. It’s an inefficient process given the amount of time required to obtain the eggs and harvest the virus within them.
THE FUTURIST: Why eggs? How does this process work?
Barnett: Basically, in the egg-based method, the virus used to make the vaccine is harvested from a fertilized hen’s egg. After the virus has accumulated in the fluid surrounding the embryo within the egg for several days, it is machine-removed, and inactivated using formalin as a detergent. Only one to two doses of vaccine can be obtained from a single egg.
THE FUTURIST: What are the prospects for expediting the production of vaccines?
Barnett: Cell-based vaccine production, a recent innovation, is more efficient. This method could take significantly less time than egg-based production. But cell-based vaccine production is not widely used throughout the pharmaceutical industry. So we are really reliant on an antiquated production method. The cell-cultured approach is considered the ideal, and it’s one that we would like to see promulgated. In the cell-based approach, the virus is injected into cells– typically mammalian kidney cells–which multiply along with the virus. Then the cells’ outer walls are removed, harvested, purified, and inactivated, using a fermentation-like process to develop a vaccine.
But the technology and scale are not there yet. Although there have been pockets of advances, it’s not a realistic option at this time.
What adds to the challenge globally is that there are relatively few companies that produce vaccines. Developing nations, which lack pharmaceutical industrial infrastructure, may not be able to access vaccines well beyond this six-month window.
THE FUTURIST: What makes this flu strain different from past strains?
Barnett: This strain has pieces of human, swine, and avian influenza. One important point to mention about this strain is that pigs serve as mixing vessels. A pig can be jointly infected by multiple species’ strains of influenza; a pig can be infected by a human strain and a bird strain, those two strains can then recombine in a pig to generate a novel strain for which there is no preexisting immunity in human populations.
We don’t know whether the H1N1 will mutate into something more severe. One concern we do have is that the 1918 pandemic was preceded by a milder influenza epidemic. It’s uncertain whether what we’re seeing today is a preliminary stage of something more severe, or whether its severity will become lesser over time. This is why local surveillance is critical, as well as state- and federal-level surveillance.
THE FUTURIST: A pandemic has been declared "imminent." What does that mean?
Barnett: There are three criteria needed for a pandemic strain to emerge: First, it has to be a novel strain against which there is no immunity among humans. The H1N1 strain meets that criterion. Second, it has to be easily transmitted. The currently circulating H1N1 strain fulfills that criterion as well. Third, it has to cause significant disease in humans. This virus has shown that it can cause significant disease among humans and death in some cases.
That is why the World Health Organization has raised its pandemic influenza threat level to five on a scale of six. We don’t know for sure whether this will become a pandemic. But that is looking increasingly likely, given that the WHO’s phase 5 refers to a situation in which a pandemic is considered “imminent.”
THE FUTURIST: You also praised Tamiflu and other antiviral drugs as good options. But you noted that they have some issues of supply and drug resistance. Some researchers have already identified a few strains of common flu that are resistant to the antiviral drug Tamiflu. How quickly could the swine flu virus mutate and become resistant to our available antiviral remedies?
Barnett: That’s the $64,000 question. We don’t know. The virus could mutate very rapidly or it might not mutate at all and not go on to become more pathogenic in more regions of the globe. We just don’t know at this point.
THE FUTURIST: In your 2006 article, you attributed a primary role to the local responders, “the workers who are going to be on the front lines of any nation’s response to pandemic.” What should local responders around the world be doing now in light of the swine flu pandemic?
Barnett: One of the most important things that need to be done at the local level is effective risk communication to citizens. Any of the basic measures we’d use for seasonal flu are also relevant to H1N1 prevention: washing your hands, and covering your mouth when you cough (and preferably coughing into your elbow rather than your hands). It is currently thought that transmission is by coughing and sneezing. Hygienic measures are the best ways local communities can reduce the spread of the virus.
Another measure that local communities can implement is social distancing. For example, a number of local jurisdictions have made the decision to cancel school for a period of time.
Every community’s responders need to undertake their own assessments of trends in terms of the spread the illness and the measures that can counter it. And some measures may be more effective in a given community than others might be. The reality is that no one locality is the same as any other. Local jurisdictions know their populations best.
Local responders need to be prepared to distribute medical supplies. In the United States, for example, the Strategic National Stockpile’s “12-hour push pack” contains antivirals and other supplies. Upon receipt of these federally stockpiled materials, local-level health departments are in a lead role for distributing these supplies to the populations in their respective jurisdictions.
The concept that all disasters begin locally has a corollary, and it’s that all diseases need to fundamentally be addressed at the local level. Local-level responders need to be making decisions tailored to the needs of their communities.
Antivirals are, at least in the immediate term, the most effective and reliable means to address the situation. Tamiflu and Relenza are effective in dealing with the current H1N1 strain.
Antivirals can be used in one of two ways; they can be used in the short term after someone has started showing symptoms, but they can be also be used prophylactically to prevent illness in the first place. Different countries, in their pandemic flu plans, have taken different prioritized approaches for use of antivirals. Some countries have taken an approach favoring use of antivirals for prophylaxis. Other countries take an approach favoring treatment. It is not a matter of a “right” or “wrong” approach for prioritizing scarce resources. The approach must be tailored for jurisdictional needs.
The very good news so far is that this influenza strain is responsive to Tamiflu and Relenza. Having said that, there is always the potential for antiviral resistance to emerge.
We really do need to see how things unfold. We have every indication that antivirals will be an efficacious measure. But we really need to see how this virus evolves or mutates into either a more or a less pathogenic strain over time.
THE FUTURIST: According to a Washington Post story, Mexican authorities first saw unusual cases of pneumonia within Mexico on April 6th but only notified the World Health Organization and the Pan American Health Organization by April 16. Do you think this 10-day waiting period was appropriate, or do you think they should have acted sooner?
Barnett: I think it is easy to look back in hindsight and criticize how one jurisdiction or region approached a situation but that’s not the most productive way to focus energy at this time. In general, my view on this is to err on the side of caution. If there is any inkling that there is an out-of-season presence of an illness, reporting is the best approach. Even if the result is a false positive, a false concern is a smaller problem. It’s of course better to report earlier rather than later.
Beyond that, we currently don’t know exactly how this strain developed. It is important that individuals let their doctors know if they are experiencing fever and upper respiratory symptoms, and have a recent history of travel to an H1N1-affected region or other exposure. It is likewise prudent that people stay away from work, for example, if they are sick and have traveled to such a place. The basic sort of public-health, altruistic principles have to come into play here--avoid exposing others to the illness if you’re sick.
We don’t know yet if such a step would be needed, but mandatory quarantining of populations is a possibility should the pathogenicity and reach of the influenza increase. I should specify that isolation and quarantining are not the same thing. Isolation is sequestration of someone who is symptomatic. Quarantining is for someone who may have been exposed to an identified case and is not yet showing symptoms, but who is nonetheless being sequestered for the safety of the community.
THE FUTURIST: What role do commercial farming methods play in preventing future outbreaks? What risks do farming practices pose insofar as exposing livestock to diseases and enabling diseases to spread?
Barnett: Large-scale commercial farming is fraught with potential public-health concerns. One of the concerns relates to zoonotic strains emanating from the large-scale livestock operations. I think the current developments should raise some discussion about the role of farming and farming practices with regard to health.
May 4, 2009