Playing Constant Catchup: Can the world respond to disease crises faster?

Helen Branswell

Dr. Gary Nabel evoked a famous quote when we spoke recently about the situation the world faces with the Zika virus, the most recent in a string of emerging infectious disease crises.

“Einstein said … the definition of insanity is doing the same thing over and over and expecting different results. What we’re doing now fits his definition of insanity,’’ said Nabel, chief scientific officer of global research and development for the pharmaceutical giant Sanofi.

There is apparently some dispute over the provenance of that quote, but that’s of no import here. The point isn’t who said it, but how apropos the observation is in the current global health context. Once more, the world finds itself with an emerging infectious disease it needs to combat, and no weapons to take into battle.

As a reporter who specializes in covering infectious diseases, I’ve watched these crises arise time and again. For me, it started with SARS, which roared out of China in early 2003 to trigger the first major outbreak of the new millennium.

I lived in Toronto at the time; it was the only city outside of Southeast Asia to suffer a full-blown outbreak of severe acute respiratory syndrome. SARS was a virus that spread poorly in the community but thrived in hospitals full of sick people. This new disease crippled Toronto’s health-care system for four months.

Then, before researchers could pinpoint ways to counteract the virus through drugs or vaccines, it was gone. If SARS were to return today, the only weapon hospitals would have at their disposal would be enhanced infection control practices.

SARS was a disaster the world wasn’t prepared for, and a disaster to which the world could not respond quickly enough. Given the global toll, both in terms of lives lost and the economic disruption, you might have thought SARS would have galvanized the world to devise systems for rapid response to disease threats. You would be wrong.

H5N1 bird flu. H7N9 bird flu. MERS, the Middle East respiratory syndrome. Ebola in West Africa. All have triggered crises. The world wasn’t prepared for any of them and still lacks the tools, if any of these pathogens happen to go global.

“We just run from one crisis to another. It’s not an optimal way to respond. Not when the stakes are so high and when so many people can either lose their lives or have their whole lives changed because of one five-day infection,” Nabel told me in an interview for STAT, the Boston-based online publication covering news about health, medicine, and scientific discovery.
 
The problem with this default approach is obvious. Because the world isn’t prepared when new diseases strike — or known diseases break out in new places (Ebola in West Africa) or act in new ways (Zika in the Americas) — the cost can be high.

After most of these outbreaks, expert panels in multiple jurisdictions published reports filled with smart ideas for strengthening global health and reducing the risks emerging infectious diseases pose. Yet here we are. Zika is surging. We are going into battle bearing no arms.

There are no antiviral drugs to cure Zika, no vaccines to prevent infection. Adding to the complicity of the situation is the fact this virus is spread by mosquitoes — a notoriously difficult vector to control.

Research teams in government-funded institutions like the National Institute of Allergy and Infectious Diseases and in private industry are working to develop a Zika vaccine. There’s hope that designs used for other projects — a West Nile virus vaccine that never made it to market, for instance — can be modified to make a Zika vaccine.

The earliest stage of trials in people could start this year, but a fully tested and licensed vaccine is still years off.

Given Zika’s explosive spread, there’s a real chance that by the time it’s ready, proving the vaccine is effective may be a challenge. The collective global experience with Zika outbreaks is limited. But the pattern seems to be that the virus spreads so quickly it burns through a large percentage of the susceptible people in a population and then moves on.

That may sound reassuring, but consider this: Untold thousands of pregnant women will be infected as the virus moves through the Americas. If a recently published case series from Brazil is correct, about 30 percent of those pregnancies may result in an infant with birth defects induced by the virus.

If the outbreak in the Americas burns out, what are the prospects for a Zika vaccine? Will the pharmaceutical industry question the profit margins and leave the project to gather dust, as they did with West Nile virus vaccines?

Nabel, who formerly ran the National Institute of Health’s Vaccine Research Center, thinks the problems associated with Zika — severe brain-related birth defects, a form of (generally temporary) paralysis called Guillain-Barré syndrome — are so profound the work will proceed.

He isn’t alone in understanding that the world’s response capacities are woefully inadequate when it comes to fighting these diseases. Others are trying to identify ways to speed up the responses to major infectious disease outbreaks, so that the world isn’t doomed to repeat the same frustrating cycle every time a new threat emerges.

The World Health Organization has been working on a strategy to galvanize research into looming disease threats. Its R&D Blueprint program is meant to help the world prepare in down times for the unknown outbreaks that will inevitably come. The idea is to keep these threats off the backburner, by finding ways to incentivize the work, tighten timelines, and establish research priorities.

That there will be more outbreaks is predictable; what will cause them is not. Case in point: In December, as part of the R&D Blueprint project, the WHO published its first list of diseases that needed urgent research attention. Eight known diseases were on the list, including Lassa and Rift Valley fevers, Ebola and Marburg and Crimean Congo hemorrhagic fever.

Despite the fact that Brazil had already sounded the alarm about Zika and microcephaly, Zika didn’t make the urgent list. Instead it was placed on a runners-up list of diseases designated as “serious.”

Dr. Jeremy Farrar, head of Britain’s Wellcome Trust charity, acknowledges there will always be events that defy prediction. But systems designed to anticipate that there will be unforeseen events should soften their blows.

“The truth is, of course, you’re never going to be able to be prepared for everything you’d wish, for every eventuality,” Ferrar, a strong proponent of finding ways to fast-track vaccines and drugs in outbreaks, told me in an interview conducted for this article. “Because obviously there’s things we know about, and there’s things we don’t know about. And the things we know about can often change…. Zika’s a very good example of that.”

Farrar thinks approaches like divvying up work — France, you’re responsible for Disease X, Britain, you take the lead on Disease Y, for instance — would help focus efforts and minimize duplication.

He also envisages the development of flexible vaccine platforms that could be adapted quickly to address new threats. Think of it as having some basic cookie recipes where you could swap raisins for chocolate chips or turn sweet shortbreads into savory ones.

Still another way researchers are hoping to speed up responses is by doing more human challenge studies — testing how a disease operates on the body by deliberately infecting people, or giving an experimental vaccine to volunteers and then exposing them to the disease agent to see if they are protected.

A consortium from the National Institutes of Health, Johns Hopkins Bloomberg School of Public Health and the University of Vermont recently used this approach to test a dengue vaccine. They hope now to use their challenge approach to expand knowledge about Zika infection.

A challenge study can only be done if the disease is mild; an ethics review board would never approve this approach for Ebola, for instance.

Regardless, there are no magic bullets here. A combination of small steps — and big money — may lead to a world where medical solutions are developed and ready to be used during a disease threat, not after.

But it will take financial commitment and sustained attention to the overall problem, not simply the racing from outbreak to outbreak approach Nabel decried.

 

ABOUT THE AUTHOR

Helen Branswell is a senior writer at STAT, where she reports on infectious diseases and global health. Helen came to STAT from The Canadian Press, where she had been the national news agency’s medical reporter for 15 years. Helen has reported on a string of global health outbreaks: SARS, in 2003; H5N1 bird flu; the 2009 H1N1 flu pandemic; Ebola; Middle East respiratory syndrome (MERS) and now Zika. She spent the summer of 2004 embedded at the Centers for Disease Control and Prevention on a CDC Knight Fellowship. She was a 2011 Nieman Global Health Fellow at Harvard, where her work focused on the polio eradication effort.

 

References

  1. Branswell H. Sanofi science chief says it’s time to ‘think big’ about global epidemics like Zika. STAT News, 17 March 2016. https://www.statnews.com/2016/03/17/zika-gary-nabel-sanofi/.
  2. Brasil P, Pereira JP Jr, Raja Gabaglia C, et al. Zika Virus Infection in Pregnant Women in Rio de Janeiro – Preliminary Report. N Engl J Med, 4 Mar 2016.
  3. Blueprint for R&D preparedness and response to public health emergencies due to highly infectious pathogens. WHO, 2015. http://www.who.int/csr/research-and-development/meeting-report-prioritization.pdf?ua=1
  4. Kirkpatrick B, Whitehead S, et al. The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model. Science Translational Medicine 2016, 8(330): 330ra36.