In 1994, journalist Laurie Garrett, in "The Coming Plague," warned of a growing threat from newly emerging health problems, especially infectious diseases, in a world increasingly vulnerable to rapid spread. Her book was highly acclaimed but apparently not widely heeded.

The book's subtitle is "Newly Emerging Diseases in a World Out of Balance." Garrett cited several factors that increase our vulnerability:

• mutating infectious organisms,
  
  
• misuse of antibiotics promoting resistant microbes,
  
  
• human encroachment into isolated areas,
  
  
• faster transmission because of extensive rapid global travel,
  
  
• distortion of resources by focused programs, and
  
  
• resources stretched thinner and over-optimized.

Current U. S. military doctrine emphasizes "net-centric" and "swarm warfare" concepts that seem to make forces much more effective. This doctrine follows from the observation, from artificial intelligence, that the cognitive effectiveness of a collective, with some simple rules of organization, can be much greater than the sum of individuals' capabilities. For example, the capability of the human brain is much greater than the sum of the capabilities of the individual neurons. So consider a "swarm warfare" analysis of infections: the microbes have been steadily losing to humans, as developments in medicine seemed to promise to banish infectious diseases entirely. They need new approaches, and they can find them simply by trying everything they can come up with and then doing more or whatever succeeds. From what we know about the new approach to warfare, we can also reason that the successful approaches are likely to involve attacking where either the defenses or the detection capabilities of the adversary — us — are weak. Therefore, the most potent invaders are likely to have many of these features:

• low lethality — don't kill hosts quickly or dramatically,
  
  
• long latency period,
  
  
• causing symptoms that are easily misdiagnosed,
  
  
• causing a stigmatized condition, so people will be reluctant to report it,
  
  
• teaming up by multiple pathogens to cause complex disorders,
  
  
• exploiting human immune system cells against the human immune system, and
  
  
• exploiting inorganic "allies" to amplify their effect.

AIDS has many of these characteristics: it does not cause death quickly; it has a long latency period (seven to 10 years); it carries stigma because of the early association with gay sex and intravenous drug use; it teams up with other pathogens (most of the fatalities are caused by infections by other organisms, such as pneumocystis pneumonia); it presents with a variety of symptoms of other disorders because of the "teaming," complicating diagnosis; and it exploits human immune cells (the virus lives in immune cells and is replicated as they multiply.)

Garrett's comment about AIDS is that it was relatively easy to detect. Because of its limited variety of spread mechanisms, it attacked readily identifiable subpopulations, at least one of which — gay men — had a community structure that facilitated information sharing and epidemiology once people started to realize that something new was happening.

What, then, would be a worse threat than AIDS? Imagine a health threat that would affect more diverse and less vocal subpopulations; that would have no subpopulation with conspicuously faster spread; and that would cause complications and effects that are less rare than Kaposi's sarcoma and pneumocystis pneumonia. If the new threat caused problems more like other, common ailments, and involved more interaction with other conditions and risk factors, possibly including interaction with inorganic factors, it would be even harder to detect than AIDS.

If it also caused conditions that are hard to treat without adverse effects, that would confound diagnosis, as diagnostic theories are confirmed or modified depending on how the conditions respond to treatment. (If your respiratory infection doesn't respond to antibiotics, your doctor is likely to modify his or her initial opinion and tell you, "it must be viral rather than bacterial." The tendency to modify diagnosis depending on response to treatment is even more widespread in treating mental disorders — that's a large part of what "Listening to Prozac" was about.)

The feedback from treatment to diagnosis also means that both diagnosis and treatment become more difficult when the indicated interventions violate social norms. An example of such an intervention would be a large-scale community quarantine, such as the one the World Health Organization imposed on Toronto to contain SARS in 2003. Another example is the attempt by pubic health officials to close gay bathhouses and discourage unprotected gay sex in the early 1980s. The latter example violated two sets of social norms: the gay community's reluctance to accept any negative information about their activities, and the general public's reluctance to acknowledge gay sexuality at all.

Difficulty obtaining treatment, either because of stigma or because of payment policies, can also interfere with efforts to identify and treat some disorders. This is why the president's commission studying mental health a few years ago recommended requiring parity in payment for mental and physical disorders.

Example: Influenza


So what might a major new threat look like? One of the most potent candidates is seemingly one of the more ordinary: a mutant strain of influenza. Flu looks like many other respiratory ailments. It seems minor at first, and people often wait to see whether it gets better before seeking treatment or altering their behavior to reduce the chance of infecting others. Given the typical three- to five-day latency period, this delay is sufficient to ensure widespread contagion for a strain that is easily transmitted human-to-human. (Avian flu, which has received much media attention, does not have this characteristic and is therefore not a major threat, unless it mutates into a more transmissible form.)

No subpopulations would be conspicuously more vulnerable, and there are interactions with other ailments (secondary respiratory infections by other organisms are common.) Perhaps most important, the most beneficial response — isolating everyone who may have been exposed — violates social norms. In fact, without a change in current public health practice, emergency rooms are likely to be the main spread vector, since they do not segregate symptomatic and asymptomatic patients. For this reason, some communities have plans to set up mobile clinics in numerous neighborhoods, or to set up temporary additional facilities separated from their emergency rooms, in the event of a pandemic. There is, however, no accepted national standard of how to respond.

This is important because influenza, just influenza, has already caused the deadliest pandemic in history — more fatalities than the Black Death (bubonic plague) in the 14th century, more than smallpox, more than malaria. Depending on which data sources one trusts, the Great Influenza of 1918 killed somewhere between 25 million and 50 million people worldwide, mostly within four months — as much as twice the total combat fatalities from World War I. It most likely started in the U.S. and spread quickly even in cities with excellent public health systems. Given its infectiousness, even good detection simply wasn't quick enough.

Unlike most other outbreaks of respiratory disease, this strain of flu had higher mortality among young, healthy adults. Retrospective analysis indicates that this strain provoked an immune response that helped kill the patient, and this effect was most pronounced in the people with the strongest immune systems. Influenza, therefore, potentially has another of the characteristics of the most serious threats: long before AIDS, at least one strain of flu found a way to turn the human immune system against itself.

Example: Depression


Another example of a health threat that could sneak up on us is depression. There is, in fact, substantial clinical evidence of an age cohort increase in incidence throughout the developed world for as long as 50 years, even after taking into account such factors as better diagnosis and increased willingness to seek treatment.

Depression certainly can be caused by multiple factors, making diagnosis and epidemiology difficult. It carries enough stigma that many people are reluctant to seek treatment, or choose to seek treatment from providers, such as clergy, who do not contribute to public health statistics. It causes death only indirectly, by potentiating suicide, dulling response to other ailments ("Maybe I should go see the doctor about this cough, but I just can't get motivated to do anything today"), and by weakening the immune system, opening the way for other illnesses.

Depression also has the characteristic of complex interaction effects of treatment. Both the condition and the medications used to treat it are associated with higher incidence of Type 2 diabetes. The mechanism is unknown, but the associations are strong enough to suggest potentiation. ("Potentiation" means "there is reason, stronger than mere statistical association, to believe A is a contributing factor to B, though not necessarily the only one and not necessarily producing the effect most of the time.")

Much stronger evidence indicates that diabetes increases the risk of heart disease. There is still stronger evidence that certain heart medications cause depression in people with no prior history of it; beta-blockers, in particular, deplete serotonin, one of the two key neurotransmitters that regulate mood.

The surprise here, in terms of usual medical thinking, is that depression might be infectious, at least in part. The evidence is too sketchy to support consensus among the medical community, but that doesn't mean much: vaccination took nearly a generation to gain acceptance, and the psychiatrists and psychologists are still trying to persuade cardiologists to monitor patients' mood, or refer them to someone else who will do so, after prescribing cardiac medications. What is known is that depression is associated with the immune system; Prozac was the first commercially successful antidepressant that was not synthesized from an antihistamine, and histamine is the key neurotransmitter that regulates immune response. That's why, if you have hay fever, which is an immune overreaction to a non-threatening invader, you take an antihistamine to counter the reaction.

There is one other connection to infection — a number of organisms are known to potentiate depression. This fact has been in medical references for decades, but psychotherapists are reluctant to publicize it because they want patients to present themselves for evaluation and let the professional do the diagnosing. More interesting, one of the organisms known to have this effect is Š influenza! From recent accounts of the 1918 pandemic, there is even some indication of a likely mechanism: people who tried to resume normal activity as soon as the fever broke had much worse outcomes than those who did not, because of both late-stage flu effects and more exposure to other infections. This means that a tendency to mope for several days after a bout with flu had survival value in a reproductive-age population, which is how genetic traits evolve.

So depression is another possible emerging threat that would be difficult to detect in time to respond appropriately, and finding the most effective responses would still be complicated.

Example: Obesity


Obesity is becoming so widespread in the developed world that health and nutrition professionals often refer to it as an epidemic. Obesity potentiates heart disease and Type 2 diabetes, among other ailments. It carries stigma, and the treatments violate social norms (the same people who tell you to lose weight are disappointed if you don't finish the meal they cooked for you.)

But is it infectious? Even medical professionals are likely to reply, "No, it's your lifestyle, stupid." But that's the advice ulcer sufferers got, a generation ago, before we learned about H. Pylori, the infectious organism that turned out to be the primary cause. There is already some respectable research implicating a couple of mutant respiratory viruses in obesity. Another possibility is that some widely used food additives have appetite-changing effects that escaped scrutiny when they were approved as safe. Surely either or both of these causes must be much more probable than a spontaneous, simultaneous lifestyle change in most of the developed world! Also, there is a trend toward excessive weight gain in large zoo animals; in view of their controlled environments and diets, this seems highly unlikely to be an effect of lifestyle choices.

So obesity, too, shows us how difficult it is to detect emerging threats and discern their likely causes.

Conclusion


So, can we detect "the coming plague"? From these examples, it is clear that we need not worry about whether an emerging health threat could sneak through our best detection systems; a few of them already have!

It is also clear that health threats will be most likely to succeed precisely when they confound conventional medical thinking. Health informatics turns out to be even more important than we thought, as does systems thinking. Therefore, improving detection of emerging health threats appears to be a subject in which some operations research analysts who have taken the time to familiarize themselves with health professionals' thinking could make an important contribution.

Finally, diseases affect whole societies, not just large numbers of people. Many historical conquests occurred, at least in part, because of superior immunity to disease. For instance, in America's war for independence, the British lost more men to malaria than to combat. Thus the topic of detecting and countering emerging health threats is, quite literally, a matter of life or death for our whole civilization.



Douglas A. Samuelson is a principal decision scientist at Serco-North America, a general professional services company in Vienna, Va. He is also president of InfoLogix, Inc., a research and consulting company in Annandale, Va., and a frequent contributor to OR/MS Today.

References

1. Laurie Garrett, 1994, "The Coming Plague: Newly Emerging Diseases in a World Out of Balance," Farrar, Straus, and Giroux; Penguin paperback, 1995.
2. John M. Barry, 2004, "The Great Influenza: The Story of the Deadliest Pandemic in History," Viking Penguin; Penguin paperback, 2005.
3. Jared Diamond, 1997, "Guns, Germs and Steel: The Fates of Human Societies," W. W. Norton.
4. Peter Kramer, 1993, "Listening to Prozac," Penguin.
5. Eva K. Lee, 2008, "In Case of Emergency," OR/MS Today, February 2008.
6. William McNeill, 1976, "Plagues and Peoples," Doubleday.
7. New Freedom Commission on Mental Health, 2003, "Achieving the Promise: Transforming Mental Health Care in America," Final Report, DHHS Pub. No. SMA-03-3832, Rockville, Md. Also available online from www.mentalhealth.samhsa.gov.
8. Douglas A. Samuelson, 1995, "Diagnosing the Real Health Care Villain," OR/MS Today, February 1995.
9. Douglas A. Samuelson, 2000, "A New Frontier? Health Services Research and Medical Informatics," OR/MS Today, February 2000.
10. Douglas A. Samuelson, 2003, "The NetWar in Iraq," OR/MS Today, June 2003.
11. Douglas A. Samuelson, "Can O.R. Help Stop 'The Invisible Plague'?" OR/MS Today, June 2004.
12. E. Fuller Torrey, 2002, "The Invisible Plague: The Rise of Mental Illness from 1750 to the Present," Free Press, 2002.
13. www.webmd.com/diet/news/20070820/obesity-virus-more-bigger-fat-cells
14. www.cdc.gov/nccdphp/dnpa/obesity/trend/
15. http://dsc.discovery.com/news/2008/03/17/zoo-animal-diet.html

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