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How to prevent a pandemic

Where did global scourges like AIDS, smallpox, cholera and the black plague come from? Most of them got their start in other animals, then made the cross-species jump to infect humans. If only we could have spotted the malicious microbes when they were just beginning to make that jump.... That's exactly what three prominent researchers are proposing we do, by establishing a global "early warning system" for infectious diseases.

The system would involve periodic testing of people who come in close contact with wild animals, ranging from zoo workers to hunters. One of the scientists says such a system could have changed the course of the global AIDS crisis ... if only it had been in place 40 years ago.

The proposal comes in an research review article written for the journal Nature by Nathan Wolfe, Claire Panosian Dunavan and Jared Diamond of the University of California at Los Angeles. Diamond is the most famous member of the trio, thanks to his best-selling books "Guns, Germs and Steel" and "Collapse: How Societies Choose to Fail or Succeed." Wolfe and Panosian Dunavan are also well-known for their work in epidemiology.

Wolfe, the recipient of an NIH Director's Pioneer Award and a member of Popular Science's "Brilliant 10" for 2005, says that setting up a sentinel system for bad bugs is a "no-brainer."

"In 100 years, when people look back on this period of history, they will say that we worked very hard to control existing pandemics, but we did very little to try to prevent future pandemics," Wolfe told me today. "Global disease control today is like cardiology was in the '50s. Instead of preventing pandemics, we wait until the 'heart attack' occurs - of course, at which time it's often too late."

In this week's Nature article, Wolfe and his colleagues recap what we've found out about the emergence of infectious diseases over the centuries. They trace five stages leading from first  cross-species transmission to human pandemic:

  • Pathogens found only in animals but not detected in humans under natural conditions - for example, most known malarial plasmodia.
  • Pathogens that are transmitted from animals to humans but not generally among humans, such as anthrax, rabies and West Nile virus.
  • Pathogens that jump from animals to humans, but appear to be transmitted among humans for only a few cycles before the outbreak dies out. The Ebola and Marburg viruses are examples.
  • Pathogens that can be transmitted from animals to humans, and also from human to human in a long outbreak cycle. This category takes in cholera, influenza A, typhus, yellow fever and dengue fever.
  • Pathogens that are passed exclusively from human to human, either because they go back to the beginnings of humanity or because the species-jumping microbe quickly evolved to become human-specific. Examples of the Stage 5 sicknesses include HIV-1 M, the virus that causes AIDS, as well as measles, mumps, rubella, smallpox and syphilis.

The researchers go on to note how infectious agents linked to animals have shaped history - for example, why indigenous Americans were vulnerable to European settlers' diseases but not vice versa (it has to do with domesticated animals, or the lack thereof).

They wind up their paper with the call to action, starting out with a proposal for an "origins initiative" to fill the gaps in our knowledge about the roots of a dozen major diseases: AIDS, cholera, dengue fever, falciparum malaria, hepatitis B, influenza A, measles, plague, rotavirus, smallpox, tuberculosis and typhoid. Pathogens from a wide range of wild and domesticated animals would be analyzed. Here's what the Nature authors say could result from such an effort:

"In addition to the historical and evolutionary significance of knowledge gained through such an origins initiative, it could yield other benefits such as: identifying the closest relatives of human pathogens; a better understanding of how diseases have emerged; new laboratory models for studying public health threats; and perhaps clues that could aid in predictions of future disease threats."

That dovetails nicely with the early warning system: 

"Most major human infectious diseases have animal origins, and we continue to be bombarded by novel animal pathogens. Yet there is no ongoing systematic global effort to monitor for pathogens emerging from animals to humans. Such an effort could help us to describe the diversity of microbial agents to which our species is exposed; to characterize animal pathogens that might threaten us in the future; and perhaps to detect and control a local human emergence before it has a chance to spread globally.

"In our view, monitoring should focus on people with high levels of exposure to wild animals, such as hunters, butchers of wild game, wildlife veterinarians, workers in the wildlife trade and zoo workers. Such people regularly become infected with animal viruses, and their infections can be monitored over time and traced to other people in contact with them."

Samples from the target groups would be analyzed for the telltale signs of emerging diseases - for example, retroviruses in the blood of bushmeat hunters. In the event of a future outbreak, public health experts could check the tissue repository to reconstruct the roots of the pathogen and come up with countermeasures.

The years-long battle against bird flu illustrates how difficult it is to fight an emerging disease - and how important the fight has become.

Eight years ago, Wolfe set up a pilot project to monitor "viral chatter" in Cameroon, by testing bushmeat hunters and their kills for blood pathogens. In the course of the project, he and his team came across three previously unknown retroviruses (that is, from the same family as HIV) and educated the hunters on safer practices for handling animals and meat.

Now Wolfe says he is "scrambling" to set up a bigger monitoring system in Cameroon as well as the Democratic Republic of Congo, Malaysia, China, Madagascar and Paraguay, using his $2.5 million in seed money from the National Institutes of Health. "The idea is that we will move out to other bilateral partners," he told me.

Wolfe said such a system might have picked up on the HIV epidemic in its earliest stages, had it been around then.

"Had we caught HIV in the '60s ... we would have been way ahead of the game. Each extra month of early warning leads to massive lives saved and financial resources preserved. You don't have to hit a home run. If you get a base hit with one of these systems, you get a huge benefit," he said.

Wolfe emphasized that the focus of such a system would be on local health authorities, with government agencies and philanthropic institutions playing a supporting role.

"What this is about is local scientists stepping up and saying, 'Look, we've got major emerging infectious diseases in our country, and we'd like to play a part,'" he said.

Eventually, the system could evolve into something of an Interpol for infectious diseases - turning national public health databases into an international whole that's greater than the sum of its parts. "This takes advantage of global public health needs," Wolfe said.

For the full story on infectious diseases and the proposed early warning system, check out this report on SciDev.net, then follow the Web link at the bottom of the report for free access to the Nature paper itself. This UCLA news release and this Wired article provide additional insights.

Is such a system too troublesome and expensive to create - or is the cost of not creating it  too great? Feel free to weigh in with your comments below.