An Interview with WHO's Dr. Mike Ryan
SARS Shows Cracks, Strengths in Disease Surveillance

Dr. Mike Ryan, coordinator of the Global Outbreak Alert and Response Network at the World Health Organization, at his office in Geneva, Switzerland.
Photo: Richard Knox, NPR

September 2003 -- NPR's Richard Knox interviewed Dr. Mike Ryan, coordinator of the Global Outbreak Alert and Response Network at the World Health Organization in Geneva, for his Sept. 23, 2003 story on WHO's disease surveillance system. The interview took place in Ryan's office at the WHO in Geneva, Switzerland. Following, an edited transcript of the interview:

Richard Knox: On July 5, WHO declared that all chains of human transmission of Severe Acute Respiratory Syndrome had been broken and that SARS had been "put back in its box." I'm told you coined that phrase. What did you mean?

Dr. Mike Ryan: When we spoke about putting SARS back in its box, we didn't understand the origin of SARS. So we had absolutely no idea if this disease could be eradicated. We understood and had a hypothesis that this disease, like many emerging diseases, probably emerged from nature. We didn't understand the natural history of the disease in an animal population. So therefore we took the approach we normally take with diseases like ebola, and that is, to focus on breaking the cycle of transmission in the human population, thereby pushing the disease back into its natural host with the hope that we could identify the natural host at some point and prevent further transfers of the disease into the human population. So in that sense, the box is like a black box. We don't exactly understand the dynamics of transmission in the natural environment. But we did believe we could put it back there and then focus on understanding how it emerged in the first place.

Knox: That's different from the way epidemiologists talk about eradicating a disease.

Ryan: Yeah, to eradicate a disease you have to understand a tremendous amount about the disease. Classically, eradication of a disease is only truly possible when the disease is purely one of humans. And for which we have an intervention which can interrupt transmission and permanently interrupt transmission. Therefore, we have to consider things like the possibility that humans could carry the disease without symptoms. If that is the case, then it's a very difficult disease to eradicate.

Knox: What are the chances that SARS is going to come out of whatever box it's in?

Ryan: We don't know. Nobody knows. If anybody thinks they know, then they're probably laboring under a misconception. What we do know of other diseases like SARS is that if a disease has a natural cycle in the environment and it emerged once into human populations, then there is a strong possibility that it can reemerge. Therefore we have to in some senses hope for the best but prepare for the worst.

Knox: If SARS returns, how are you going to detect it amidst all the cases of flu and pneumonia that will be occurring around the world in the coming months? It seems like an insurmountable problem.

Ryan: There is a real problem of signal-to-noise. We know that there's a tremendous amount of background atypical pneumonia that goes on in every country on a yearly basis. Most countries have thousands and thousands [of cases] every year. Somewhere like Hong Kong could have 20,000 -- 30,000 cases of what is described as atypical pneumonia. Which has many many causes -- some viral, some bacterial causes of disease. So therefore it is difficult and it will be difficult to pick out from all of that background noise the signal that SARS has begun again. Certainly, picking out an individual case of SARS from all that background noise, without a very very good diagnostic test is going to be extremely difficult. However, even without a diagnostic test that's absolutely foolproof, we did detect the last SARS outbreak. We detected it through the detection of clusters of atypical pneumonia, particularly in the health care environment. And certainly our first line of defense must be the kind of surveillance we can put in place in the hospital environment to pick out clusters of unusual pneumonia, particularly in the zones of emergence or in the areas close to China.

Knox: What's the problem with current diagnostic tests?

Ryan: The problem is that definitive tests are only confirmatory very late in the course of illness. We can't afford to hang around that long waiting for a confirmation of the diagnosis. So health authorities are going to have to make judgments on whether their public health system should be thrown into a response to a suspected cluster of SARS cases --- all the time understanding that there's a potential for the boy who cried wolf. If a given hospital in Singapore or Hong Kong or China ends up with 50 or 60 alerts that turn out not to be SARS then there's an element of exhaustion and complacency that can set in. If you pull the trigger time and time again without it being SARS, by the time you truly get a SARS case everybody has become complacent. And so setting that trigger is exceptionally difficult to do.

Knox: Both the Chinese and WHO have been trying for months now to pin down the origin of SARS. Why is it so elusive?

Ryan: There is a sense that if you just go out there and bleed every animal in the country you'll eventually find the source. That's not so, because infectious diseases occur in an ecological context. It may have something to do with our interaction with the animals. It may have something to do with the way we commercialize that animal source. And right now we have some indications of animals who may act as hosts, for example, civet cats. But what we have to understand is: Are these wild civet cats? Are these farmed civet cats? Are these cats being infected in markets or are they being infected in the natural environment? The other thing we have to try and understand is: Was this just a once-off event in which a particular mutant escaped into the human population? And is not likely to further emerge? Is this going to be a recurrent transfer of disease into human populations?

We have to understand a lot more about the virus that infects animals and compare that virus to the virus that infects humans. Are they the same virus? Is there a significant difference between the two? And we have to look at animal handlers to see if humans are being infected on a regular basis. Animal handlers often get the diseases of the animals they handle. In most cases that results in subclinical infection. And you may find that animal handlers would have a high prevalence of infection or a high prevalence of antibodies in their blood to the virus. That doesn't necessarily mean that they've ever become sick and it doesn't necessarily mean that that's a problem for the broader human population. But what happened? This is a big question. What happened in the natural environment? And what happened at the animal-human interface to create the conditions where by we had these explosions of cases in the community and within hospital environments? And we really donít understand that adequately.

Knox: What's the likelihood that the SARS virus may be lurking in humans at undetectable levels? That it might not need to be reintroduced from animals?

Ryan: That's a good point. Certainly there is another scenario for reemergence. And that is if there were a human carrier condition where individuals could carry the disease unbeknownst to themselves and pass it on to others. For me that's increasingly less likely because we're now two to three months since the breaking of the chain of transmission of SARS. If there were a significant carrier state or if there were significant subclinical transmission, I believe at this point we would have seen amplification at the hospital level or in the community or in certain risks groups. And we haven't see that so far.

But you can never be certain about these things. Because the dynamics of transmission of a disease or of a newly emerging disease are that the patterns of transmission remain quite unstable at that interface for a period. And very often it takes years or even generations for a new infectious disease to settle down into a pattern of transmission in humans. We see this with many diseases. People say "diseases of childhood." Well, why are diseases "diseases of childhood?" Very often they're because the infectious agent has reached a point where it has infected most of the adult population. And the newly available susceptible populations are those that are being born every year. So it usually becomes usually a milder disease of childhood, where all the new susceptibles are mopped up when they're born or very early in childhood. That's one expression of the adaptation of the organism to the human life cycle.

You also see settling down in patterns not just in terms of the age groups affected but you also see a settling down in patterns in terms of seasonality. If the transmission of a given disease is facilitated by certain climatic conditions, eventually you see that pattern emerge. You see a disease of winter or a disease of spring or a disease of summer emerge. Or you see patterns that spread out over years, so they're not seasonal but they're temporal.You get outbreaks every number of years. Again, we see that with measles now because we've introduced vaccination. We generally only vaccinate 80 or 90 percent of the population. So over a period of eight or 10 or 15 years, we keep missing 10 percent, 10 percent every year. Well, then all of a sudden we build up a group in the population unprotected. And you very often see large epidemics in a cycle every four, five or 10 years. So sometimes we force the temporality on the disease by our interventions.

It may be that if SARS reemerges, it could reemerge once, twice or three times -- any number of times -- before it would settle down into some stable pattern of transmission among human beings. And we really don't know and nobody knows yet.

Knox: WHO's management of the SARS outbreak is widely viewed as a success, even though it did spread to more than 30 countries. If you have to deal with SARS-2, what will be your definition of success this time around?

Ryan: If SARS reemerges, I would like to see it contained in the district in which it reemerges. If not the district, then the province in which it reemerges. And if not the province, the country that it reemerges. That's the concept of containment. If we get to the point where we again see three, four, five countries implicated in a SARS outbreak, then, you know, it's questionable whether that represents a true success. Even if we do contain it. I'd like to see the performance at a much higher level this time. I'd like to see the disease contained in the country in which it reemerges. If not, damn close to that point. I certainly wouldn't like to see the situation with 30 countries affected.

Knox: WHO's Global Alert and Response Network has been going for several years. But SARS really put it on the map. How do you intend to capitalize on that?

Ryan: There's a lot to do. We can't over-focus on SARS. SARS is a great lesson. SARS is a shot across our bows. But it's not the only player in the park. And we have to realize that whatever we invest in in terms of public health preparedness has to have a capacity not only to respond to one particular virus but to respond to any emergence of any new disease. And that's a huge developmental task.

If you look at it, you've got a situation where sovereign states protect their national interests and their national borders by a massive investment, usually in a military force. We have internalized the concept of national security. And we need now to look at health as a security issue. We need governments to understand that someone with a gun on your border is not the only threat to your national security. Thereís another significant threat to national security which can occur inside your country, which is the emergence of a disease that can disrupt your economy, collapse your health care system. And I think countries should actually sit down and do a simple mathematical equation, and compare the threats that they face. Countries build armies because they fear invasion. And they spend a lot of money in making sure everyone else understands that they shall not be invaded. I wonder are we spending even half of one percent of that in most countries in protecting our health security. As displayed by SARS, disease is a much greater threat to your national security -- and to your economy.